Systems and methods for selectively occluding the superior vena cava for treating heart conditions

ABSTRACT

Systems and methods and devices are provided for treating conditions such as heart failure and/or pulmonary hypertension by at least partially occluding flow through the superior vena cava for an interval spanning multiple cardiac cycles. A catheter with an occlusion device is provided along with a controller that actuates a drive mechanism to provide at least partial occlusion of the patient&#39;s superior vena cava, which reduces cardiac filling pressures, and induces a favorable shift in the patient&#39;s Frank-Starling curve towards healthy heart functionality and improved cardiac performance. The occlusion device may include a lumen obstructed by a relief valve that may permit fluid flow through the occlusion device to release an excessive build-up of pressure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/168,357, filed Oct. 23, 2018, now U.S. Pat. No. 10,842,974, whichclaims priority to U.S. Provisional Application Ser. No. 62/642,569,filed Mar. 13, 2018, and U.S. Provisional Application Ser. No.62/576,529, filed Oct. 24, 2017, and which is also acontinuation-in-part of U.S. patent application Ser. No. 15/753,300,filed Feb. 17, 2018, now U.S. Pat. No. 10,758,715, which is a nationalstage application of PCT/US2016/047055, filed Aug. 15, 2016, which is acontinuation-in-part of U.S. patent application Ser. No. 15/203,437,filed Jul. 6, 2016, now U.S. Pat. No. 10,279,152, which is acontinuation of U.S. patent application Ser. No. 14/828,429, filed Aug.17, 2015, now U.S. Pat. No. 9,393,384, the entire contents of each ofwhich are incorporated herein by reference.

FIELD OF THE INVENTION

The disclosure relates to methods and systems for improving cardiacfunction in patients suffering from heart failure, including patientswith reduced ejection fraction, and for treating pulmonary hypertensionand/or cardiorenal syndrome.

BACKGROUND OF THE INVENTION

Heart failure is a major cause of global mortality. Heart failure oftenresults in multiple long-term hospital admissions, especially in thelater phases of the disease. Absent heart transplantation, the long termprognosis for such patients is bleak, and pharmaceutical approaches arepalliative only. Consequently, there are few effective treatments toslow or reverse the progression of this disease.

Heart failure can result from any of multiple initiating events. Heartfailure may occur as a consequence of ischemic heart disease,hypertension, valvular heart disease, infection, inheritedcardiomyopathy, pulmonary hypertension, or under conditions of metabolicstress including pregnancy. Heart failure also may occur without a clearcause—also known as idiopathic cardiomyopathy. The term heart failureencompasses left ventricular, right ventricular, or biventricularfailure.

While the heart can often initially respond successfully to theincreased workload that results from high blood pressure or loss ofcontractile tissue, over time this stress induces compensatorycardiomyocyte hypertrophy and remodeling of the ventricular wall. Inparticular, over the next several months after the initial cardiacinjury, the damaged portion of the heart typically will begin to remodelas the heart struggles to continue to pump blood with reduced musclemass or less contractility. This in turn often leads to overworking ofthe myocardium, such that the cardiac muscle in the compromised regionbecomes progressively thinner, enlarged and further overloaded.Simultaneously, the ejection fraction of the damaged ventricle drops,leading to lower cardiac output and higher average pressures and volumesin the chamber throughout the cardiac cycle, the hallmarks of heartfailure. Not surprisingly, once a patient's heart enters thisprogressively self-perpetuating downward spiral, the patient's qualityof life is severely affected and the risk of morbidity skyrockets.Depending upon a number of factors, including the patient's priorphysical condition, age, sex and lifestyle, the patient may experienceone or several hospital admissions, at considerable cost to the patientand social healthcare systems, until the patient dies either of cardiacarrest or any of a number of co-morbidities including stroke, kidneyfailure, liver failure, or pulmonary hypertension.

Currently, there are no device-based solutions that specifically targeta reduction in preload to limit the progression of heart failure.Pharmaceutical approaches are available as palliatives to reduce thesymptoms of heart failure, but there exists no pharmaceutical path toarresting or reversing heart failure. Moreover, the existingpharmaceutical approaches are systemic in nature and do not address thelocalized effects of remodeling on the cardiac structure. It thereforewould be desirable to provide systems and methods for treating heartfailure that can arrest, and more preferably, reverse cardiac remodelingthat result in the cascade of effects associated with this disease.

Applicants note that the prior art includes several attempts to addressheart failure. Prior to applicants' invention as described herein, thereare no effective commercial devices available to treat this disease.Described below are several known examples of previously known systemsand methods for treating various aspects of heart failure, but noneappear either intended to, or capable of, reducing left ventricular enddiastolic volume (“LVEDV”), left ventricular end diastolic pressure(“LVEDP”), right ventricular end diastolic volume (“RVEDV”), or rightventricular end diastolic pressure (“RVEDP”) without causing possiblysevere side-effects.

For example, U.S. Pat. No. 4,546,759 to Solar describes a triple ballooncatheter designed for placement such that a distal balloonintermittently occludes the superior vena cava, a proximal balloonintermittently occludes the inferior vena cava, and an intermediateballoon expands synchronously with occurrence of systole of the rightventricle, thereby enhancing ejection of blood from the right ventricle.The patent describes that the system is inflated and deflated insynchrony with the normal heart rhythm, and is designed to reduce theload on the right ventricle to permit healing of injury or defect of theright ventricle. It does not describe or suggest that the proposedregulation of flow into and out of the right ventricle will have aneffect on either LVEDV or LVEDP, nor that it could be used to arrest orreverse acute/chronic heart failure.

U.S. Patent Publication No. US 2006/0064059 to Gelfand describes asystem and method intended to reduce cardiac infarct size and/ormyocardial remodeling after an acute myocardial infarction by reducingthe stress in the cardiac walls. The system described in the patentincludes a catheter having a proximal portion with an occlusion balloonconfigured for placement in the inferior vena cava and a distal portionconfigured for placement through the tricuspid and pulmonary valves intothe pulmonary artery. The patent application describes that by partiallyoccluding the inferior vena cava, the system regulates the amount ofblood entering the ventricles, and consequently, reduces the load on theventricles, permitting faster healing and reducing the expansion of themyocardial infarct. The system described in Gelfand includes sensorsmounted on the catheter that are read by a controller to adjustregulation of the blood flow entering the heart, and other measuredparameters, to within predetermined limits. The patent application doesnot describe or suggest that the system could be used to treat, arrestor reverse congestive heart failure once the heart has already undergonethe extensive remodeling typically observed during patient re-admissionsto address the symptoms of congestive heart failure.

U.S. Patent Publication No. US 2010/0331876 to Cedeno describes a systemand method intended to treat congestive heart failure, similar in designto described in Gelfand, by regulating the return of venous bloodthrough the inferior vena cava. The system described in Cedeno describesthat a fixed volume balloon disposed in the inferior vena cava willlimit blood flow in the inferior vena cava (IVC). The degree ofocclusion varies as the vessel expands and contracts during inspirationand expiration, to normalize venous blood return. The patent applicationfurther describes that the symptoms of heart failure improve withinthree months of use of the claimed system. Although the system andmethods described in Cedeno appear promising, there are a number ofpotential drawbacks to such a system that applicants' have discoveredduring their own research. Applicants have observed during their ownresearch that fully occluding the inferior vena cava not only reducesleft ventricular volume, but significantly reduces left ventricularsystolic pressure, leading to reduced systemic blood pressure andcardiac output. Moreover, full inferior vena cava occlusion may increasevenous congestion within the renal, hepatic, and mesenteric veins;venous congestion is a major cause of renal failure in congestive heartfailure patients.

There are several major limitations to approaches that involve partialor full occlusion of the IVC to modulate cardiac filling pressures andimprove cardiac function. First, the IVC has to be reached via thefemoral vein or via the internal jugular vein. If approached via thefemoral vein, then the patient will be required to remain supine andwill be unable to ambulate. If approached via the jugular or subclavianveins, the apparatus would have to traverse the superior vena cava andright atrium, thereby requiring cardiac penetration, which predisposesto potential risk involving right atrial injury, induction ofarrhythmias including supraventricular tachycardia or bradycardia due toheart block. Second, the IVC approach described by Cedeno and colleaguesdepends on several highly variable indices (especially in the setting ofcongestive heart failure): 1) IVC diameter, which is often dilated inpatients with heart failure; b) intermittent (full or partial) IVCocclusion may cause harm by increasing renal vein pressure, whichreduces glomerular filtration rates and worsens kidney dysfunction; c)dependence on the patient's ability to breathe, which is often severelyimpaired in HF (A classic breathing pattern in HF is known as CheynesStokes respiration, which is defined by intermittent periods of apneawhere the IVC may collapse and the balloon will cause complete occlusionresulting in lower systemic blood pressure and higher renal veinpressure); d) if prolonged cardiac unloading is required to see aclinical improvement or beneficial changes in cardiac structure orfunction, then IVC occlusion will not be effective since sustained IVCocclusion will compromise blood pressure and kidney function. Third, theapproach defined by Cedeno will require balloon customization dependingon IVC size, which may be highly variable. Fourth, many patients withheart failure have IVC filters due to an increased propensity for deepvenous thrombosis, which would preclude broad application of IVCtherapy.

Pulmonary hypertension (PH) is also a major cause of morbidity andmortality worldwide. While heart failure is a common cause of pulmonaryhypertension, as mentioned above, pulmonary hypertension may also becaused by primary lung disease. Today, pharmacologic treatments mayreduce pulmonary artery systolic pressure (PASP) and improve symptomsand ultimately survival for patients with pulmonary hypertension.However, there are drawbacks to pharmacologic treatments such as costsand side effects.

In view of the foregoing drawbacks of the previously known systems andmethods for regulating venous return to address heart failure, it wouldbe desirable to provide systems and methods for treating acute andchronic heart failure that reduce the risk of exacerbatingco-morbidities associated with the disease.

It further would be desirable to provide systems and methods fortreating acute and chronic heart failure that arrest or reverse cardiacremodeling, and are practical for chronic and/or ambulatory use.

It still further would be desirable to provide systems and methods fortreating heart failure that permit patients suffering from this diseaseto have improved quality of life, reducing the need for hospitaladmissions and the length of hospital stays, and the associated burdenon societal healthcare networks.

It also would be desirable to provide systems and methods that permittreatment of pulmonary hypertension and cardiorenal syndrome.

SUMMARY OF THE INVENTION

In view of the drawbacks of the previously known systems and methods fortreating heart failure, it would be desirable to provide systems andmethods for treating acute and/or chronic heart failure that can arrest,and more preferably, reverse cardiac remodeling that result in thecascade of effects associated with this disease.

It further would be desirable to provide systems and methods forarresting or reversing cardiac remodeling in patients suffering fromheart failure that are practical for ambulatory and/or chronic use.

It still further would be desirable to provide systems and methods fortreating heart failure that reduce the risk of exacerbatingco-morbidities associated with the disease, such as venous congestionresulting in renal and hepatic complications.

It also would be desirable to provide systems and methods for treatingheart failure that permit patients suffering from this disease to haveimproved quality of life, while reducing the need for hospitalre-admissions and the associated burden on societal healthcare networks.

It further would be desirable to provide systems and methods fortreating pulmonary hypertension that permit patients suffering from thisdisease to have improved quality of life. In addition, it would bedesirable to provide systems and methods for treating heart attacks,acute heart failure, chronic heart failure, heart failure with preservedejection fraction, right heart failure, constrictive and restrictivecardiomyopathies, and cardio-renal syndromes (Types 1-5).

These and other advantages are provided by the present invention, whichprovides systems and methods for regulating venous blood return to theheart through the superior vena cava (“SVC”), over intervals spanningseveral cardiac cycles, to reduce ventricular overload, and to reducecardiac preload and pulmonary artery pressure without increasing renalvein pressure. In accordance with the principles of the presentinvention, venous regulation via the SVC can be used to reduce LVEDP,LVEDV, RVEDP, and/or RVEDV, and to arrest or reverse ventricularmyocardial remodeling. Counter-intuitively, applicants have observed inpreliminary animal testing that intermittent partial occlusion of theSVC does not lead to stagnation of cerebral flow or observable adverseside effects. More importantly, applicants' preliminary animal testingreveals that occlusion of the SVC results in significant reduction inboth RVEDP and LVEDP, while improving total cardiac output and without asignificant reduction on left ventricular systolic pressure (“LVSP”).Accordingly, unlike the approach discussed in the foregoing publishedCedeno patent application, the present invention provides a beneficialreduction in LVEDP, LVEDV, RVEDP, and/or RVEDV, with negligible impacton LVSP, but improved stroke volume (cardiac output), and reduced riskfor venous congestion resulting in increased co-morbidities. The systemsand methods described herein provide acute improvement in cardiacfilling pressures and function to benefit patients at risk for acutelydecompensated heart failure.

There are several major advantages to targeting SVC flow (instead of IVCflow). First, device placement in the SVC avoids use of the femoralveins and avoids cardiac penetration. This allows for development of afully implantable, and even ambulatory, system for acute or chronictherapy. Second, SVC occlusion can be intermittent or prolongeddepending on the magnitude of unloading required. Unlike IVC occlusion,prolonged SVC occlusion maintains systemic blood pressure and improvescardiac output. This allows for sustained unloading of both the rightand left ventricle, which allows for both acute hemodynamic benefit andthe potential for long term beneficial effects on cardiac structure orfunction. Third, unlike IVC occlusion, SVC occlusion does not depend onpatient respiration. Fourth, by developing an internal regulator of SVCocclusion driven by mean right atrial pressure or the pressuredifferential across the occlusion balloon, the SVC device can beprogrammed and personalized for each patient's conditions. Fifth, byplacing the device in the SVC, the device can be used in patients withexisting IVC filters.

In accordance with another aspect of the present invention, partial ortotal intermittent occlusion of the SVC over multiple cardiac cycles isexpected to permit the myocardium to heal, such that the reduced wallstress in the heart muscle arrests or reverses the remodeling that issymptomatic of the progression of heart failure. Without wishing to bebound by theory, applicants believe that intermittent occlusion of theSVC permits the heart, when implemented over a period of hours, days,weeks, or months, to transition from a Starling curve indicative ofheart failure with reduced ejection fraction towards a Starling curvehaving LVEDP and LVEDP more indicative of normal cardiac function.Consequently, applicant's preliminary animal testing suggests that useof the inventive system over a period of hours, days, weeks, or months,e.g., 3-6 months, may not only arrest the downward spiral typical of thedisease, but also may enable the heart to recover function sufficientlyfor the patient to terminate use of either the system of the presentinvention, pharmaceutical treatments, or both.

In accordance with another aspect of the disclosure, a system isprovided that comprises a catheter having a flow limiting elementconfigured for placement in or on the SVC, and a controller forcontrolling actuation of the flow limiting element. The controller ispreferably programmed to receive an input indicative of fluctuations inthe patient's hemodynamic state and to regulate actuation/deactivationof the flow limiting element responsive to that input. The fluctuationsin the patient's hemodynamic state may result from the patient'sambulatory activity. The controller may be programmed at the time ofimplantation of the catheter to retain full or partial occlusion of theSVC over a predetermined number of heart cycles or predetermined timeinterval based on the patient's resting heart rate, and this presetnumber of cycles or time interval may be continually adjusted by thecontroller responsive to the patient's heart rate input. The controllermay further receive signals from sensors and/or electrodes indicative ofsensed parameters reflecting the hemodynamic state, e.g., blood flowrate, blood volume, pressure including cardiac filling pressure, and thecontroller may continually adjust the preset number of cycles or timeinterval responsive to the sensed parameter(s).

In one preferred embodiment, the catheter is configured to be implantedintravascularly (e.g., via the patient's left subclavian vein), so thatthe flow limiting element is disposed within the SVC just proximal ofthe right atrium. A proximal end of the catheter may be coated orimpregnated with an antibacterial agent to enable prolonged use of thecatheter with reduced risk of infection at the site where the catheterpasses percutaneously. The controller preferably is battery-powered, andincludes a quick-connect coupling that permits the actuation mechanismof the controller to operatively couple to the flow limiting element. Ina preferred embodiment, the controller is sufficiently small such thatit may be worn by the patient in a harness around the shoulder. Incontrast to previously-known systems, which tether the patient to a bedor acute-care setting, the system of the present invention is configuredso that the patient can be ambulatory and go about most dailyactivities, thereby enhancing the patient's quality-of-life andimproving patient compliance with the course of treatment using theinventive system. In one embodiment, the controller is configured forimplantation at a suitable location within the patient, e.g.,subcutaneously under the clavicle. In such an embodiment, theimplantable controller is configured for bidirectional communicationwith an external controller, e.g., mobile device or system-specificdevice. The external controller may be configured to charge the batteryof the implantable controller, e.g., via respective inductive coils ineach controller, and may receive data indicative of the sensedparameters including heart rate, blood flow rate, blood volume, pressureincluding cardiac filling pressure. One or more external power sourcesmay be in electrical communication with the implantable controller andalso may be configured to provide power to the controller to charge thebattery of the implantable controller. The one or more external powersources may generate an alert when a power level of the one or moreexternal power sources is below a threshold power level.

In a preferred embodiment, the flow limiting element comprises anon-compliant or semi-compliant balloon or balloons affixed to a distalregion of the catheter, such that the controller actuates the balloon byperiodically inflating and deflating the balloon to selectively fully orpartially occlude the SVC and/or the azygos vein. For example, thecontroller may be programmed to intermittently actuate the flow limitingelement to at least partially occlude the SVC for a first predeterminedtime interval and to contract for a second predetermined time intervalover multiple cardiac cycles. The first predetermined time interval maybe at least five times greater than the second predetermined timeinterval. For example, the first predetermined time interval may be 4-6minutes, while the second predetermined time interval is 1-30 seconds.In alternative embodiments, the flow limiting element may comprisemembrane covered umbrellas, baskets or other mechanical arrangementcapable of being rapidly transitioned between deployed and contractedpositions, e.g., by a driveline connected to the controller. In stillfurther embodiments, the flow limiting element may take the form of abutterfly valve or ball valve, provided the flow limiting element doesnot create stagnant flow zones in the SVC when in the contracted or openposition. In yet further embodiments, the flow limiting elementcomprises a cuff configured to be applied to the exterior of the SVC andoperates by narrowing or occluding the SVC when inflated.

The inventive system may include a sensor disposed on the catheter forplacement within the venous or arterial vasculature to measure thepatient's heart rate or blood pressure. The sensor preferably generatesan output signal that is used as an input to the controller to adjustthe degree or timing of the occlusion created by the flow limitingelement. In another embodiment, the controller may be configured tocouple to a third-party heart rate or blood pressure sensor, such asthose typically used by sporting enthusiasts, e.g., the Fitbit, viaavailable wireless standards, such as Bluetooth, via the patient'ssmartphone. In this embodiment, the cost, size and complexity of thecontroller may be reduced by integrating it with commercially availablethird-party components.

In accordance with another aspect of the disclosure, a method forcontrolling blood flow in a patient comprises inserting and guiding tothe vena cava of a patient a venous occlusion device, coupling theocclusion device to a controller worn externally by, or implanted in,the patient; and activating the venous occlusion device intermittently,for intervals spanning multiple cardiac cycles, so that over a period ofseveral minutes, hours, days, weeks, or months, remodeling of themyocardium is arrested or reversed.

In accordance with another aspect of the disclosure, a system for use incombination with a ventricular assist device (VAD) for improvingefficiency and functionality of the VAD, and for reducing the risk ofadverse effects of the VAD, is provided. The system includes a catheterhaving a proximal end and a distal region, the catheter sized and shapedfor placement (e.g., intravascular placement, such as through asubclavian or jugular vein of the patient) so that the distal region isdisposed in a superior vena cava (SVC) of the patient. The system alsoincludes a flow limiting element, e.g., an SVC occlusion balloon,disposed on the distal region of the catheter, the flow limiting elementselectively actuated to at least partially occlude the SVC, and acontroller operatively coupled to the catheter to intermittently actuatethe flow limiting element to at least partially occlude the SVC for aninterval spanning a single or multiple cardiac cycles, thereby reducingcardiac preload and pulmonary artery pressure to improve cardiacperformance. For example, the controller may reduce cardiac preloadduring the interval sufficiently to improve cardiac performance asmeasured by at least one of: reduced cardiac filling pressures,increased left ventricular relaxation, increased left ventricularcapacitance, increased left ventricular stroke volume, increasedlusitropy, reduced left ventricular stiffness or reduced cardiac strain.

The system further may include a first pressure sensor disposed on thecatheter proximal to the flow limiting element, the first pressuresensor outputting a first pressure signal, and a second pressure sensordisposed on the catheter and distal to the flow limiting element, thesecond pressure sensor outputting a second pressure signal, wherein thecontroller generates a first signal corresponding to a differencebetween the first pressure signal and the second pressure signal, thefirst signal indicative of a degree of occlusion of the flow limitingelement. The controller may use the first signal to determine when toactuate the flow limiting element to at least partially occlude the SVCand when to cease actuation of the flow limiting element. The controlleralso may be programmed to activate an alarm as a safety signal for theoperator based on the first signal. In one embodiment, the controller isconfigured for implantation at a suitable location within the patient,e.g., subcutaneously under the clavicle.

In addition, the controller may be programmed to intermittently actuatethe flow limiting element to at least partially occlude the SVC for afirst predetermined time interval and to contract for a secondpredetermined time interval over multiple cardiac cycles. The firstpredetermined time interval may be at least ten times greater than thesecond predetermined time interval. For example, the first predeterminedtime interval may be 4-6 minutes, while the second predetermined timeinterval is 1-10 seconds.

In one preferred embodiment, the flow limiting element is an inflatablecylindrical balloon, the inflatable cylindrical balloon having a reliefvalve coupled to the inflatable cylindrical balloon having an open andclosed position. The relief valve may be opened at a predeterminedpressure between 30-60 mmHg to permit fluid to flow through the SVC to aright atrium of the patient. The system further may include an azygosvein occlusion balloon disposed on the catheter proximal to the flowlimiting element. The azygos vein occlusion balloon may be selectivelyactuated to at least partially occlude an azygos vein of the patient,and the azygos vein occlusion balloon and the SVC occlusion balloon maybe independently actuated. In addition, the system permits operation ofthe VAD at slower speeds to achieve a hemodynamic response equivalent toor greater than a VAD-only hemodynamic response at higher speeds

In addition, the system may include a left ventricular assist device(LVAD), the LVAD including a catheter having a proximal end and a distalregion, the distal region having an inflow end and an outflow end, thecatheter sized and shaped for placement through a femoral artery of thepatient so that the inflow end is disposed in a left ventricle of thepatient and the outflow end is disposed in an aorta of the patient. TheLVAD also includes a pump, e.g., an impeller pump, disposed on thedistal region of the catheter, wherein the pump may be selectivelyactuated to pump blood from the left ventricle through the inflow endand expel blood into the aorta via the outflow end, and an LVADcontroller operatively coupled to the LVAD to actuate the pump to pumpblood from the left ventricle to the aorta, thereby unloading the leftventricle and increasing coronary and systemic perfusion. The LVADcontroller operatively coupled to the catheter of the system mayregulate the activation and deactivation of the flow limiting element toat least partially occlude the SVC simultaneously as the LVAD controlleractuates the pump to pump blood from the left ventricle to the aorta.

Alternatively or in addition to, the system may further include a rightventricular assist device (RVAD), the RVAD including a pump, e.g., animpeller pump, that may be selectively actuated to pump blood from theSVC through an inflow end of the RVAD and expel blood into a pulmonaryartery via an outflow end of the RVAD. The controller also may beoperatively coupled to the RVAD to actuate the pump to pump blood fromthe SVC to the pulmonary artery, thereby unloading the right ventricle.For example, the controller may actuate the flow limiting element to atleast partially occlude the SVC simultaneously as the controlleractuates the pump to pump blood from the SVC to the pulmonary artery.

In another preferred embodiment, the RVAD includes a catheter having aproximal end and a distal region, the distal region having an inflow endand an outflow end, the catheter sized and shaped for placement througha femoral vein of the patient so that the outflow end is disposed in apulmonary artery of the patient and the inflow end is disposed in an IVCof the patient. The RVAD also includes a pump, e.g., an impeller pump,disposed on the distal region of the catheter, wherein the pump may beselectively actuated to pump blood from the IVC through the inflow endand expel blood into the pulmonary artery via the outflow end, and anRVAD controller operatively coupled to the RVAD to actuate the pump topump blood from the IVC to the pulmonary artery, thereby unloading theright ventricle. The RVAD controller operatively coupled to the catheterof the system may regulate the activation and deactivation of the flowlimiting element to at least partially occlude the SVC simultaneously asthe RVAD controller actuates the pump to pump blood from the IVC to thepulmonary artery.

BRIEF DESCRIPTION OF THE DRAWINGS

The characteristics and advantages of the present invention will becomeapparent from the detailed description of the embodiment of thedisclosure presented below in conjunction with the attached drawings, inwhich:

FIG. 1A is a frontal, partially broken-away view of the major arteriesand veins of the heart.

FIG. 1B illustrates the vena cava including major veins associated withthe vena cava.

FIGS. 2A and 2B illustrate Frank-Starling curves for normal andafflicted cardiac conditions.

FIG. 3 is a graph of exemplary pressure-volume loop curves of leftventricular pressure versus left ventricular volume throughout a cardiaccycle for a patient having normal cardiac function and a patientsuffering from congestive heart failure.

FIG. 4A is a schematic drawing of a system constructed in accordancewith the principles of the present invention.

FIG. 4B is a schematic drawing of an implantable system constructed inaccordance with the principles of the present invention.

FIG. 4C is a drawing of a power source and a charging base.

FIGS. 5A-5B are schematic drawings of the catheter of FIG. 4A and FIG.4B wherein the flow limiting element comprises a cylindrical balloonwith modified anchoring members shown in its expanded and contractedstates, respectively.

FIG. 6 is a schematic drawing of the catheter of FIG. 4A and FIG. 4Bwherein the flow limiting element comprises a mechanically actuatedmembrane covered basket.

FIG. 7 is a cross-sectional view of the catheter of FIG. 4A and FIG. 4B.

FIGS. 8A and 8B are schematic drawings of a flow limiting elementcomprising a ball-shaped balloon shown in its expanded and contractedstates, respectively.

FIGS. 9A and 9B are schematic drawings of a flow limiting elementcomprising a spring-loaded plug shown in its expanded and contractedstates, respectively.

FIGS. 10A and 10B are schematic drawings of a flow limiting elementcomprising an alternative embodiment of a spring-loaded plug shown inits expanded and contracted states, respectively.

FIG. 11 shows graphs and a table showing left ventricle (LV) pressureand LV volume for a number of successive heart beats in a swine modelfollowing full occlusion of the inferior vena cava (IVC).

FIG. 12 shows graphs and a table showing LV pressure and LV volume for anumber of successive heart beats in a swine model following partialocclusion of the superior vena cava (SVC).

FIGS. 13-14 are graphs showing the changes in pressure as a function ofleft and right ventricular volume, respectively, during occlusion of thesuperior vena cava (SVC) and release in a swine subjected to heartfailure in accordance with the principles of the present invention.

FIGS. 15-22 show test results for swine subjects subjected to heartfailure.

FIGS. 23A to 23D illustrate, respectively, clinical pressure changes inleft ventricular end diastolic pressure, left ventricular end systolicpressure, left ventricular volume and ventricular stroke work during thedeflation time of a one minute episode of continuous SVC occlusion inaccordance with the principles of the present invention.

FIGS. 24A to 24D illustrate, respectively, clinical pressure changes inleft ventricular end diastolic pressure, left ventricular end systolicpressure, left ventricular volume and ventricular stroke work during thedeflation time of a five minute episode of continuous SVC occlusion inaccordance with the principles of the present invention.

FIGS. 25A to 25D illustrate, respectively, clinical pressure changes inleft ventricular end diastolic pressure, left ventricular end systolicpressure, left ventricular volume and ventricular stroke work during thedeflation time of a ten minute episode of continuous SVC occlusion inaccordance with the principles of the present invention.

FIGS. 26A to 26C illustrate, respectively, clinical pressure changes inpulmonary capillary wedge pressure, pulmonary artery pressure and rightatrial pressure observed during a five minute episode of continuous SVCocclusion in accordance with the principles of the present invention.

FIGS. 27A to 27E illustrate, respectively, clinical pressure changes insystolic pressure, diastolic pressure, mean arterial pressure, meanpulmonary artery pressure, and mean pulmonary capillary wedge pressureduring five minutes of continuous SVC occlusion in accordance with theprinciples of the present invention.

FIGS. 28A to 28B illustrate, respectively, clinical pressure changes inmean pulmonary artery pressure and mean arterial pressure, during tenminutes of continuous SVC occlusion in accordance with the principles ofthe present invention.

FIG. 29 illustrates the cardiac output before occlusion and duringocclusion of the SVC in accordance with the principles of the presentinvention.

FIG. 30 illustrates the pulmonary artery systolic pressure during withocclusion and without occlusion of the SVC in accordance with theprinciples of the present invention.

FIG. 31 is a prophetic example of how SVC occlusion in accordance withthe principles of the present invention is expected to change the courseof the disease.

FIG. 32 is a perspective view of the cylindrical flow limiting element.

FIG. 33 is a cross-sectional view of the cylindrical flow limitingelement showing the relief valve.

FIGS. 34A-B are cross-sectional views of the cylindrical flow limitingelement having binary and gradual relief valves.

FIG. 35 is a top view of the cylindrical flow limiting element having arelief valve in a closed position.

FIGS. 36A-B are top views of the cylindrical flow limiting elementhaving a binary relief valve and a gradual relief valve in an openposition.

FIGS. 37A-B are perspective and cutaway views of the cylindrical flowlimiting element engaged with a stent.

FIGS. 38A-B are top views of the cylindrical flow limiting elementhaving a balloon occluder in an inflated and deflated position.

FIGS. 39A-B are top views of the cylindrical flow limiting elementhaving a cylindrical balloon occluder in an inflated and deflatedposition.

FIGS. 40A-B are perspective and cutaway views of a stent coupled to arelief valve.

FIG. 41 is a cutaway view of a cylindrical flow limiting element coupledto a filter.

FIG. 42A is a cutaway perspective view of a cylindrical flow limitingelement coupled to a catheter with a sensor and FIG. 42B is an exemplaryphasic curve.

FIG. 43 is a view of an introducer sheath entering an SVC, a flowlimiting element within the SVC, and a catheter positioned within theheart.

FIG. 44 is a view of an introducer sheath positioned within an SVC, aflow limiting element incorporated in the introducer sheath, and acatheter positioned within the heart.

FIG. 45 is a view of an occlusion system having an azygos vein occlusionballoon and a second occlusion balloon positioned within the SVC.

FIG. 46 is a view of an occlusion cuff wrapped around the SVC.

FIGS. 47A-B are views of an exterior side and an interior side of anocclusion cuff, and FIGS. 47C-D are perspective views of an occlusioncuff.

FIG. 48 is an alternative exemplary system constructed in accordancewith the principles of the present invention.

FIG. 49 illustrates an SVC occlusion system in combination with atrans-valvular LVAD.

FIG. 50 is a graph illustrating enhancement of the unloading capacity ofSVC occlusion when used in combination with a trans-valvular LVAD.

FIG. 51 illustrates an SVC occlusion system in combination with atrans-valvular RVAD.

FIG. 52 illustrates an SVC occlusion system in combination with analternative trans-valvular RVAD.

FIG. 53 illustrates an SVC occlusion system in combination with an LVAD.

FIG. 54 illustrates an SVC occlusion system in combination with anintra-aortic balloon pump (IABP).

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1A and 1B, the human anatomy in which the presentinvention is designed for placement and operation is described ascontext for the system and methods of the present invention.

More particularly, referring to FIG. 1A, deoxygenated blood returns toheart 10 through vena cava 11, which comprises superior vena cava 12 andinferior vena cava 13 coupled to right atrium 14 of the heart. Bloodmoves from right atrium 14 through tricuspid valve 15 to right ventricle16, where it is pumped via pulmonary artery 17 to the lungs. Oxygenatedblood returns from the lungs to left atrium 18 via the pulmonary vein.The oxygenated blood then enters left ventricle 19, which pumps theblood through aorta 20 to the rest of the body.

As shown in FIG. 1B, superior vena cava 12 is positioned at the top ofvena cava 11, while inferior vena cava 13 is located at the bottom ofthe vena cava. FIG. 1B also shows azygos vein 16 and some of the majorveins connecting to the vena cava. As noted herein, occlusion of theinferior vena cava 13 may pose risks of venous congestion, and inparticular, potential blockage or enlargement of the hepatic veinsand/or suprarenal vein that may worsen, rather than improve, thepatient's cardiovascular condition and overall health.

In accordance with one aspect of the present invention, applicants havedetermined that selective intermittent occlusion of the superior venacava (“SVC”) poses fewer potential adverse risks than occlusion of theinferior vena cava (“IVC”). Moreover, applicants' animal and humantesting reveals that controlling the return of venous blood to the rightventricle by partially or fully occluding the SVC beneficially lowersRVEDP, RVEDV, LVEDP and LVEDV without adversely reducing leftventricular systolic pressure (LVSP).

Applicants understand that selective intermittent occlusion of the SVCwill reduce the risk of worsening congestion of the kidneys, which is amajor cause of ‘cardio-renal’ syndrome, as compared to IVC occlusion.Cardio-renal syndrome is impaired renal function due to volume overloadand neurohormonal activation in patients with heart failure. Volumeoverload may occur where the weakened heart cannot pump as much blood,which leads to less blood flow through the kidneys. With less blood flowthrough the kidneys, less blood is filtered by the kidneys and lesswater is released via urination causing excess volume to be retained inthe body. With the excess volume, the heart pumps with increasingly lessefficiency and the patient ultimately spirals toward death as the bodybecomes progressively more congested.

Applicants understand that IVC occlusion generally reduces the bloodflow through the kidneys as the occluded IVC increases pressure in therenal vein, thereby reducing the kidneys ability to filter out fluid.IVC occlusion further causes blood to back-up and otherwise preventsdeoxygenated blood from returning to the heart. As a result, renalfunction may too be reduced, worsening congestion. However, SVCocclusion ultimately increases flow to the kidneys thereby improvingrenal function. Specifically, by reducing flow into the right atrium viaSVC occlusion, volume within the left ventricle is ultimately reduced,permitting the muscle fibers to stretch within a normal range, naturallyincreasing contractility and allowing the heart to drive more fluid tothe kidneys. The kidneys may then extract water, which may be removedfrom the body through urination. It is further understood that duringSVC occlusion, a negative pressure sink is created in the right atriumcaused by an abrupt reduction in right atrial pressure and volume. As aresult, flow from the renal vein may be accelerated thereby enhancingrenal decongestion and promoting blood flow across the kidney,increasing urine output. Accordingly, SVC occlusion may benefit patientswith heart failure and/or cardiorenal syndrome by reducing cardiac andpulmonary pressures and promoting decongestion.

In addition, implantation in the SVC permits a supra-diaphragmaticdevice implant that could not be used in the IVC without cardiacpenetration and crossing the right atrium. Further, implantation of theoccluder in the SVC avoids the need for groin access as required by IVCimplantation, which would limit mobility making an ambulatory deviceimpractical for short term or long term use. In addition, minor changesin IVC occlusion (time or degree) may cause more dramatic shifts inpreload reduction and hence total cardiac output/systemic blood pressurewhereas the systems and methods of the present invention as expected topermit finely tuned decrease in venous return (preload reduction).

Applicants understand that intermittent occlusion of the SVC (i.e.,cardio-pulmonary unloading) over a period of time (e.g., minutes, hours,days, weeks, or months) will beneficially permit a patients' heart todiscontinue or recover from remodeling of the myocardium. Applicants'animal and human testing indicates that the system enables themyocardium to transition from pressure-stroke volume curve indicative ofheart failure towards a pressure-stroke volume curve more closelyresembling that of a healthy heart.

In general, the system and methods of the present invention may be usedto treat any disease to improve cardiac function by arresting orreversing myocardial remodeling, and particularly those conditions inwhich a patient suffers from heart failure. Such conditions include butare not limited to, e.g., systolic heart failure, diastolic(non-systolic) heart failure, decompensated heart failure patients in(ADHF), chronic heart failure, acute heart failure and pulmonaryhypertension, heart attacks, heart failure with preserved ejectionfraction, right heart failure, constrictive and restrictivecardiomyopathies, and cardio-renal syndromes (Types 1-5). The system andmethods of the present invention also may be used as a prophylactic tomitigate the aftermath of acute right or left ventricle myocardialinfarction, pulmonary hypertension, RV failure, post-cardiotomy shock,or post-orthotopic heart transplantation (OHTx) rejection, or otherwisemay be used for cardiorenal applications and/or to treat renaldysfunction, hepatic dysfunction, or lymphatic congestion. Also, thesystem and methods of the present invention may reduce hospital stayscaused by various ailments described herein, including at least acuteexacerbation.

The relationship between left ventricular pressure or left ventricularvolume and stroke volume is often referred to as the Frank-Starlingrelationship, or “Starling curve” and is illustrated in FIGS. 2A-2B.That relationship states that cardiac stroke volume is dependent onpreload, contractility, and afterload. Preload refers to the volume ofblood returning to the heart; contractility is defined as the inherentability of heart muscle to contract; and afterload is determined byvascular resistance and impedance. In heart failure due to diastolic orsystolic dysfunction, reduced stroke volume leads to increased volumeand pressure increase in the left ventricle, which can result inpulmonary edema. Increased ventricular volume and pressure also resultsin increased workload and increased myocardial oxygen consumption. Suchover-exertion of the heart results in worsening cardiac function as theheart becomes increasingly deprived of oxygen due to supply and demandmismatch. Furthermore, as volume and pressure build inside the heart,contractile function worsens due to stretching of cardiac muscle. Thiscondition is termed “congestive heart failure.”

Referring to FIG. 2A, a series of Starling curves are illustrated, inwhich topmost curve (curve 1) depicts functioning of a normal heart. Asshown in the curve, stroke volume increases with increasing LVEDP orLVEDV, and begins to flatten out, i.e., the slope of the curvedecreases, only at very high pressures or volumes. A patient who hasjust experienced an acute myocardial infarction (“AMI”), as indicated bythe middle curve (curve 2), will exhibit reduced stroke volume at everyvalue of LVEDV or LVEDP. However, because the heart has just begun toexperience the overload caused by the localized effect of the infarct,myocardial contractility of the entire ventricle is still relativelygood, and stroke volume is still relatively high at low LVEDP or LVEDV.By contrast, a patient who has suffered from cardiac injury in the pastmay experience progressive deterioration of cardiac function as themyocardium remodels over time to compensate for the increased workloadand reduced oxygen availability, as depicted by the lowermost curve(curve 3) in FIG. 2A. As noted above, this can lead to progressivelylower stroke volume as the ventricle expands due to generally highervolume and pressure during every phase of the cardiac cycle. As will beobserved from comparison of curves 1 and 3, the stroke volume continuesto decline as the LVEDP or LVEDV climb, until eventually the heart givesout or the patient dies of circulatory-related illness.

FIG. 2B provides an alternative formulation of a Frank-Starling curve,curve 6, illustrating the differences between functioning of a healthyheart and one in heart failure. Line 7, up to point 8, illustrates aFrank-Starling curve for a normal healthy heart As discussed withrespect to FIG. 2A, for a normal heart, as the end-diastolic volumeincreases, the stroke volume increases. For a healthy heart, however,beyond point 8, increased end-diastolic volume no longer results inincreased stroke volume, and continued increases in end-diastolic volumedo not result in further increases in stroke volume. This phenomenon isshown that the solid flat line that extends substantially horizontallybeyond point 8. Decreasing dotted line 9, which extends beyond 8, inFIG. 2B, represents a Frank-Starling curve for a patient in heartfailure. Dotted line 9 indicates that for patients with heart failure,further increases in end-diastolic volume do not result in asubstantially flat stroke volume, but instead stroke volume decreases.Accordingly, increasing EDV for patients with HF results in furtherreduction in SV, leading to a downward spiral in heart function, andultimately death. FIG. 2B reflects a phenomenon referred to as“diastolic ventricular interaction,” which arises in part due to thestructural arrangement of the cardiac chambers. As discussed, forexample, in an article entitled “Diastolic ventricular interaction inchronic heart failure,” Lancet 1997; 349:1720-24 by J. Atherton et al.,the pericardium constrains the extent to which the ventricles of afailing heart can expand. Consequently, as right ventricular enddiastolic volume increases, it necessarily causes a reduction in the enddiastolic volume of the left ventricle. As reported in that article,reduction in right ventricular diastolic filling caused by externallower body suction allows augmented left ventricular diastolic filling.

Applicants understand that the foregoing phenomenon can advantageouslybe utilized in the context of the present invention to improve cardiacperformance. In particular, in heart failure and the presence ofpulmonary hypertension, right ventricular congestion due to increasedvolume overload can push the interventricular septum towards the leftventricular cavity, thereby reducing LV stroke volume and cardiacoutput. By occluding flow through the SVC, right ventricular pressureand volume are reduced. This in turn will shift the interventricularseptum away from the LV cavity, allowing for increased left ventricularstroke volume and enhanced cardiac output. For these reasons, SVCocclusion in accordance with the principles of the present invention mayfavorably alter diastolic ventricular interaction and enhance cardiacoutput. Specifically, with respect to diastolic heart failure, SVCocclusion in accordance with the principles of the present invention mayprovide a reduction in cardiac filling pressures, increased LVrelaxation (tau), increased LV capacitance, increased lusitropy, reducedLV stiffness, and reduced cardiac strain. The effect of the SVCocclusion of the present invention can thus be visualized as shiftingdotted line 9 of Frank-Starling curve 6 in FIG. 2B for a patient inheart failure towards lower EDV, which in effect moves the cardiacperformance upwards and closer towards the flat portion of the curvethat extends beyond point 8 for a healthy patient. The system andmethods of inducing at least partial intermittent SVC occlusion of thepresent invention for patients in HF therefore improves heart functionby moving a patient's heart contractility toward a healthy range of thepatient's Frank-Starling curve.

FIG. 3 illustratively shows pressure-volume loops for a normal heart,labeled “normal”, corresponding to curve 1 in FIG. 2B, and a heartsuffering from congestive heart failure, labeled “CHF” (curve 3 in FIG.2B). For each loop, the ventricular volume and pressure at the end ofdiastole correspond to the lower-most, right-most corner of the loop(point A), while the upper-most, left-most corner of each loopcorresponds to the beginning systole (point B). The stroke volume foreach pressure-volume loop corresponds to the area enclosed within theloop. Accordingly, the most beneficial venous regulation regime is onethat reduces the volume and pressure at point A while not also causingnegligible reduction in point B, thereby maximizing the stroke volume.

In accordance with one aspect of the present invention, the system andmethods are designed, over the course of hours, days, weeks, or months,to shift or transition the Starling curve of the patient's heartleftwards on the diagram of FIG. 2B (or to move the pressure-volume loopin FIG. 3 leftwards and downwards). This may be accomplished byintermittently fully or partially occluding the SVC to reduce the volumeand hence pressure of blood entering the right ventricle, and which mustthen be pumped by the left ventricle. Applicants' preliminary animaltesting indicates that such intermittent occlusion, maintained overseveral cardiac cycles, reduces the workload and wall stress in themyocardium throughout the cardiac cycle, reduces myocardial oxygenconsumption, and improves contractile function.

Referring now to FIG. 4A, exemplary system 30 of the present inventionis described. System 30 includes catheter 31 having flow limitingelement 32 coupled to controller 33 programmed to intermittently actuateflow limiting element 32. As discussed below, system 30 optionally maybe configured to transfer information bi-directionally with conventionalcomputing device 45 such as a smartphone, laptop, smartwatch, or tablet,illustratively an Apple iPhone 5 or iPad, available from Apple Inc.,Cupertino, Calif., on which a special-purpose application has beeninstalled to communicate and/or control controller 33.

Preferably, catheter 31 comprises a flexible tube having distal portion34 configured for placement in the SVC. Distal portion 34 includes flowlimiting element 32 that, in use, is disposed in superior vena cava 12(see FIG. 1B) of a patient to selectively impede blood flow into rightatrium 14. In this embodiment, flow limiting element 32 illustrativelycomprises a balloon capable of transitioning between a contracted state,allowing transluminal placement and an expanded, deployed state. Flowlimiting element 32 preferably is sized and shaped so that it partiallyor fully occludes flow in the SVC in the expanded state. Catheter 31 iscoupled at proximal end 35 to controller 33, which houses drivemechanism 36 (e.g., motor, pump) for actuating flow limiting element 32,processor 37 programmed to control signals to drive mechanism 36, andoptional sensor 42 for monitoring a physiologic parameter of thepatient, such as heart rate or blood pressure.

Controller 33 may include source of inflation medium 48 (e.g., gas orfluid) and drive mechanism 36 may transfer the inflation medium betweenthe source and flow limiting element 32 responsive to commands fromprocessor 37. When flow limiting element 32 is inflated with inflationmedium, it partially or fully occludes venous blood flow through theSVC; when the inflation medium is withdrawn, flow limiting element 32deflates to remove the occlusion, thereby permitting flow to resume inthe SVC. Flow limiting element 32 may be a balloon that preferablycomprises a compliant or semi-compliant material, e.g., nylon, whichpermits the degree of expansion of the balloon to be adjusted toeffectuate the desired degree of partial or complete occlusion of theSVC. In addition, catheter 31, when partially external, provides afail-safe design, in that flow limiting element 32 only can be inflatedto provide occlusion when the proximal end of catheter 31 is coupled tocontroller 33. Such a quick-disconnect coupling 40 at proximal end 35permits the catheter to be rapidly disconnected from controller 33 forcleaning and/or emergency.

Controller 33 preferably also includes power supply 39 (e.g., battery)that provides the power needed to operate processor 37, drive mechanism36 and data transfer circuit 38. Controller 33 may be sized and of sucha weight that it can be worn in a harness under the patient's clothing,so that the system can be used while the patient is ambulatory or suchthat controller 33 may be implanted within the patient. As discussedherein below, processor 37 includes memory 41 for storing computersoftware for operating the controller 33. Controller 33 may beconfigured for implantation at a suitable location within the patient,e.g., subcutaneously under the clavicle. In such an embodiment, theimplantable controller is configured for bidirectional communicationwith an external controller, e.g., computing device 45 orsystem-specific device. An external controller may be used to charge thebattery of the implantable controller, e.g., via respective inductivecoils in or coupled to each controller, and may receive data indicativeof the sensed parameters resulting from the patient's ambulatoryactivity including heart rate, blood flow rate, blood volume, pressureincluding cardiac filling pressure.

In one embodiment, data transfer circuit 38 monitors an input from anexternal sensor, e.g., positioned on catheter 31, and provides thatsignal to processor 37. Processor 37 is programmed to receive the inputfrom data transfer circuit 38 and adjust the interval during which flowlimiting element 32 is maintained in the expanded state, or to adjustthe degree of occlusion caused by flow limiting element 32. Thus, forexample, catheter 31 may have optional sensor 42 positioned withindistal portion 34 of the catheter to measure parameters, e.g., heartrate, blood flow rate, blood volume, pressure including cardiac fillingpressure and central venous pressure. The output of sensor 42 is relayedto data transfer circuit 38 of controller 33, which may pre-process theinput signal, e.g., decimate and digitize the output of sensor 42,before it is supplied to processor 37. The signal provided to processor37 allows for assessment of the effectiveness of the flow limitingelement, e.g., by showing reduced venous pressure during occlusion andduring patency, and may be used for patient or clinician to determinehow much occlusion is required to regulate venous blood return based onthe severity of congestion in the patient. Additionally, sensor 43 maybe included on catheter 31 proximal to flow limiting element 32, tomeasure parameters, e.g., heart rate, blood flow rate, blood volume,pressure including cardiac filling pressure and central venous pressure.Sensor 43 may be used to determine the extent of occlusion caused byelement 32, for example, by monitoring the pressure drop across the flowlimiting element.

As another example, catheter 31 may include electrodes 44 for sensingthe patient's heart rate. Applicants understand that it may be desirableto adjust the interval during which occlusion of the SVC is maintainedresponsive to the patient's ambulatory activities, which typically willbe reflected in the patient's hemodynamic state by a sensedphysiological parameter(s), e.g., heart rate, blood flow rate, bloodvolume, pressure including cardiac filling pressure and/or centralvenous pressure. Accordingly, electrodes 44 may provide a signal to datatransfer circuit 38, which in turn processes that signal for use by theprogrammed routines run by processor 37. For example, if the occlusionis maintained for a time programmed during initial system setup toreflect that the patient is resting, e.g., so that flow limiting elementis deployed for 5 seconds and then released for two seconds before beingre-expanded, it may be desirable to reduce the occluded time interval to4 seconds or more depending upon the level of physical activity of thepatient, as detected by a change in heart rate, blood flow rate, bloodvolume, pressure including cardiac filling pressure and/or centralvenous pressure above or below predetermined thresholds. Alternatively,processor 37 may be programmed to maintain partial or full occlusion inthe SVC for a preset number of cardiac cycles determined at the time ofinitial implantation of the catheter. Sensor inputs provided to datatransfer circuit 38, such as hemodynamic state, also may be used toadjust the duty cycle of the flow limiting element responsive to thepatient's detected level of activity. In addition, processor 37 may beprogrammed to maintain partial or full occlusion in the SVC for a presetnumber of cardiac cycles after adjustment to the predetermined occlusioninterval is made.

Data transfer circuit 38 also may be configured to providebi-directional transfer of data, for example, by including wirelesscircuitry to transfer data from controller 33 to an external unit fordisplay, review or adjustment. For example, data transfer circuit mayinclude Bluetooth circuitry that enables controller 33 to communicatewith patient's computing device 45. In this manner, controller may sendinformation regarding functioning of the system directly to computingdevice 45 for display of vital physiologic or system parameters using asuitably configured mobile application. In addition, the patient mayreview the data displayed on the screen of computing device 45 anddetermine whether he or she needs to seek medical assistance to addressa malfunction or to adjust the system parameters. Further, the mobileapplication resident on computing device 45 may be configured toautomatically initiate an alert to the clinician's monitoring servicevia the cellular telephone network.

Optionally, data transfer circuit 38 may be configured to synchronize toreceive data from other mobile applications on computing device 45, andthus reduce the cost and complexity of the inventive system. Forexample, a number of third party vendors, such as Fitbit, Inc., SanFrancisco, Calif., market monitors that measure physiologic parametersin real time, such as the Charge HR wristband monitor, that measuresphysical activity and heart rate. In accordance with one aspect of thedisclosure, data transfer circuit 38 can be programmed to receive aninput from such a third-party monitor via wireless communication withcomputing device 45, and that processor 37 may be programmed to controlactivation of drive mechanism 36 responsive to that input. In thisembodiment, the catheter need not include optional sensor 42, sensor 43or electrodes 44, thereby greatly simplifying the construction ofcatheter 31 and coupling 40.

Catheter 31 may include anchor member 46 configured to anchor flowlimiting element 32 within the SVC. Anchor member 46 may be contractiblefor delivery in a contracted state and expandable upon release from adelivery device, e.g., a sheath. Anchor member 46 may be coupled tocatheter proximal or distal to flow limiting element 32 and/or may becoupled to flow limiting element 32. The system shown in FIG. 4A mayeffectively shift a patient's heart contractility into a healthy rangeof the Frank-Starling curve illustrated in FIG. 2A.

Referring now to FIG. 4B, controller 33 is shown implanted at a suitablelocation within the patient. As is illustrated in FIG. 4B, externalpower source 47 may be configured to charge power supply 39 (e.g.,battery) of the implantable controller. For example, external powersource 47 may transcutaneously charge power supply 39 via respectiveinductive coils. External power source 47 may be integrated intoclothing or a harness worn by the patient. Specifically, external powersource 47 may be placed in a pocket or holder configured to receiveexternal power source 47. When the garment or harness is worn by thepatient, the pocket or holder may be designed to place external powersource 47 in close proximity to battery 39 for efficient transcutaneouscharging. More than one external power source 47 may be integrated intothe garment to provide additional power. The one or more external powersources may be permanently integrated into the garment or harness or maybe removably engaged with the garment or harness such that each may beindividually removed and attached. For example, two external powersources 47 may be integrated into specially designed pockets of vest 64as is illustrated in FIG. 4B. Vest 64 may include wire 66 incorporatedinto vest 64 to permit electrical communication between the two externalpower sources.

Power source 47 may generate an alert when an available power supplyreaches or falls below a certain threshold power level. For example,power source 47 may have a visual indicator and/or an auditory indicatorfor providing a warning to the patient or caregiver. The visualindicator may be an LED light system or a display embedded into asurface of power source 47 that visually provides information regardingthe available power supply. The auditory indicator may be a speakerembedded into power source 47 that sounds an alarm when the availablepower supply reaches a certain threshold. A signal indicating that theavailable power supply of power source 47 has reached a certainthreshold also may or alternatively be communicated directly to anexternal device, e.g. computing device 45, and/or to controller 33 andthen from controller 33 to an external device, e.g. computing device 45,which may be programmed to initiate a visual or audio alert. Anadditional power source 47 may supply power to power supply 39 when theprimary power source runs out of power to ensure power can becontinuously provided to power supply 39. Power source 47 may include aprocessor with memory for transcutaneously transmitting and receivingdata from processor 37. The processor of power source 47 may be used toreprogram processor 37 and/or store information about operatingparameters to be later downloaded by an external device, e.g. computingdevice 45.

Each external power source 47 may be placed in electrical communicationwith a wall power outlet or base charger 65 shown in FIG. 4C to chargethe external power source. Base charger 65 may be in electricalcommunication with a wall power outlet and may be configured to chargeone or more external power sources 47 at the same time. To permit powersupply 39 continuous access to a power source, external power sources 47may be periodically disengaged from the vest and charged such that atleast one external power source 47 is in electrical communication withpower supply 39 while the other external power source 47 is beingcharged in base charger 65. Also, by enabling the system to interfacewith commercially available heart rate monitors and smartphones and/ortablets, the system provides both reduced cost and reduced complexity.

Referring now to FIGS. 5A and 5B, an exemplary embodiment of catheter31′ is described, wherein catheter 31′ is constructed similarly tocatheter 31 of FIG. 4A and FIG. 4B except with a modified anchor. Asshown in FIG. 5A when flow limiting element 32′ is in an expanded, fullyoccluding state, and shown in FIG. 5B, when flow limiting element 32′ isin a contracted state, catheter 31′ may include radially expandinganchoring arms 49. Anchoring arms 49 are configured to radially expand,e.g., when exposed from a delivery sheath, to contact the inner wall ofsuperior vena cava 12 and anchor flow limiting element 32′ therein.

Referring now to FIG. 6 , an alternative embodiment is described whereinthe occlusion may comprise a wire basket. Flow limiting element 50 maybe formed of a biocompatible material, such as nickel-titanium orstainless steel, and comprises plurality of axially or spirallyextending wires 51 that are biased to expand radially outward whencompressed. Flow limiting element 50 preferably includes a biocompatiblemembrane covering, so that it partially or fully occludes flow in theSVC in the expanded state. Wires 51 may be coupled at distal end 52 todistal end 53 of actuation wire 54, and affixed to ring 55 at theirproximal ends 56. Ring 55 is disposed to slide on actuation wire 54 sothat when actuation wire 54 is pulled in the proximal direction againstsheath 57 (see FIGS. 5A and 5B), wires 51 expand radially outward. Asshown in FIG. 5B, in response to a force applied to the proximal end ofactuation wire 54 by drive mechanism 36, actuation wire 54 is retractedproximally against sheath 57 of the catheter; transitioning flowlimiting element 50 to its expanded deployed state. Conversely, whendrive mechanism 36 is deactivated, spring force applied by wires 51pulls actuation wire 54 in the proximal direction, thereby enablingwires 51 to return to their uncompressed state, lying substantially flatagainst actuation wire 54. As noted above, flow limiting element 50 hasa “fail safe” design, so that the flow limiting element resumes thecollapsed, contracted state shown in FIG. 5A when catheter 31 isuncoupled from drive mechanism 36. In this embodiment, drive mechanism36 may be a motor, which may be a linear motor, rotary motor,solenoid-piston, or wire motor.

Flow limiting element 50 may be constructed so that it is biased to thecontracted position when catheter 31 is disconnected from controller 33,so that flow limiting element 50 can only be transitioned to theexpanded, deployed state when the catheter is coupled to controller 33and the processor has signaled drive mechanism 36 to expand the flowlimiting element.

Referring now to FIG. 7 , catheter 31 preferably includes at least threelumens 60, 61, 62. Lumen 60 may be used as an inflation lumen and/or forcarrying actuation wire 54 that extends between flow limiting element32/50 and the drive mechanism 36 of controller 33. Lumen 61 permitsoptional sensors 42, 43 or electrodes to communicate with data transfercircuit 38, and optional lumen 62 for delivering a pharmacological agent(e.g., a drug) to the heart.

In operation, catheter 31 with flow limiting element 32/50 is insertedinto the patient's subclavian vein and guided to the SVC of the patient,e.g., to a position proximal of the entrance to the right atrium (seeFIG. 1A). Techniques known in the art can be used to insert and fix flowlimiting element 32/50 at the desired venous location in the patient.Proper localization of the device may be confirmed using, for example,vascular ultrasound. Alternatively, flow limiting element 32/50 may beinserted through the jugular vein or even a peripheral vein and guidedto the SVC under fluoroscopic or ultrasound guidance.

Once catheter 31 and flow limiting element 32/50 are positioned at thedesired locations, controller 33 initiates a process in which theocclusion element is expanded and contracted such that blood flow in theSVC is intermittently occludes and resumed. The extent to which the flowlimiting element impedes blood flow can be regulated by adjusting thedegree to which the flow limiting element expands radially, and also fortime interval for the occlusion, e.g., over how many heart beats. Forexample, in some embodiments the flow limiting element may impede bloodflow in the SVC by anywhere from at least 50% up to 100%. Impedance ofblood flow may be confirmed using methods known in the art, e.g., bymeasuring reductions in pressure, reductions in pressure fluctuations,or visually using ultrasound.

In accordance with one aspect of the disclosure, controller 33 includessoftware stored in memory 41 that controls the timing and duration ofthe successive expansions and contractions of flow limiting element32/50. As described above, the programmed routines run by processor 37may use as an input the patient's cardiac cycle. For example, in someembodiments, the software may be configured to actuate flow limitingelement 32/50 to maintain partial or complete occlusion of the SVC overmultiple cardiac cycles, for example, four or more successive heartbeats in the subject. Controller 33 may accept as input via datatransfer circuit 38 an output of electrodes 44 representative of thepatient's electrocardiogram (ECG), or alternatively may receive such aninput wirelessly from a third-party heart rate application running onthe patient's smartphone, such that the software running on processor 37can adjust the interval and/or degree of the occlusion provided bysystem 30 responsive to the patient's heart rate. Thus, for example, ifthe patient is physically active, the timing or degree of occlusioncaused by the flow limiting element may be reduced to permit fasterreplenishment of oxygenated blood to the patient's upper extremities.Conversely, if the heart rate indicates that the patient is inactive,the degree of occlusion of the SVC may be increased to reduce theresting workload on the heart. Alternatively, or in addition, system 30may accept an input via data transfer circuit 38 a value, measured byoptional sensors 42 and 43, or a third party application and device,such as a blood pressure cuff, representative of the patient's bloodpressure, such that controller 33 regulates flow through the SVCresponsive to the patient's blood pressure.

Controller 33 may be programmed to cause the flow limiting element toexpand when a sensed parameter is outside a predetermined range and/orabove or below a predetermined threshold. For example, controller 33 maycause the flow limiting element to expand when right atrium (“RA”)pressure is sensed by optional sensors 42 and/or 43 to be within apredetermined range, e.g., 15 to 30 mmHg, 18 to 30 mmHg, 20 to 30 mmHg,20 to 25 mmHg, or above a predetermined threshold, e.g., 15 mmHg, 18mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. As another example, controller33 may cause the flow limiting element to expand when the mean pulmonaryartery (“PA”) pressure is sensed by optional sensors 42 and/or 43 to bewithin a predetermined range, e.g., 15 to 30 mmHg, 18 to 30 mmHg, 20 to30 mmHg, 20 to 25 mmHg, or above a predetermined threshold e.g., 15mmHg, 18 mmHg, 20 mmHg, 22 mmHg, 25 mmHg, 30 mmHg. The predeterminedrange and/or the predetermined threshold may be patient specific andcontroller 33 may be programmed and reprogrammed for individualpatients.

Referring now to FIGS. 8-10 , alternative forms of intravenous flowlimiting elements suitable for use to occlude the SVC are described. Aswill be apparent to one skilled in the art, while FIGS. 4-6 depict acylindrical flow limiting element, other shapes may be used. Inaddition, while not illustrated with anchoring members in FIGS. 8-10 ,anchoring members may be included. In each pair of drawings, 8A, 8B, 9A,9B and 10A, 10B, the pair-wise drawings depict that each flow limitingelement has a collapsed contracted state (FIGS. 8A, 9A and 10A), wherethe flow limiting element does not significantly impede blood flow, andan expanded deployed state (FIGS. 8B, 9B and 10B), in which the flowlimiting element partially of fully occludes blood flow through the SVC.

In particular, referring to FIGS. 8A and 8B, catheter 70 includesballoon 71 attached to distal end 72. Balloon 71 is illustrated ashaving a rounded ball shape.

Referring now to FIGS. 9A and 9B, catheter 80 includes flow limitingelement 81 comprising spring-loaded plug 82 formed of a biocompatiblematerial (e.g., beryllium) and having a tapered conical shape.Spring-loaded plug 82 is captured in its collapsed contracted statewithin sheath 83 disposed at distal end 84 of catheter 80. Moreparticularly, a vertex of conically-shaped plug 82 is positionedadjacent the proximal end 85 of sheath 83. During delivery of catheter80, spring-loaded plug 82 is captured within sheath 83 in itslow-profile state to allow blood flow in the SVC. To expandspring-loaded plug 82, force is applied via actuation wire 86 towithdraw plug 82 from sheath 83. As for the previous embodiments, plug82 is biased to return within sheath 83 when the proximal force isremoved from the proximal end of actuation wire 86, so that the flowlimiting element 81 remains in its collapsed contracted state ifdisconnected from controller 33.

Referring to FIGS. 10A and 10B, catheter 90 depicts a furtheralternative embodiment of occlusive device 91, which takes the form ofspring-loaded plug 92. Spring-loaded plug 92 is similar to plug 82 ofFIGS. 9A and 9B, and has a tapered conical shape and is loaded withinsheath 93 disposed at distal end of catheter 90. In response to adistally-directed force applied by drive mechanism 36 to the proximalend of catheter 90, spring-loaded plug 92 is pushed out of distal end ofsheath 94 and expands to occlude the SVC. When the distally-directedforce is removed, spring-loaded plug 92 retracts to its collapsedcontracted state within sheath 94, thereby permitting blood to flowsubstantially unimpeded through the SVC.

Applicants have observed that animal testing indicates that a systemconstructed and operated in accordance with the methods of the presentSVC occlusion system provides significant benefits over previously-knownIVC systems for treating heart failure. Preliminary animal testingconducted on swine models one week post myocardial infarction isdescribed below.

Referring to FIG. 11 , changes in the LV pressure and LV volume areshown for a number of successive heart beats in a swine model followingfull occlusion of the inferior vena cava (IVC), as suggested in theforegoing published Cedeno patent application. In particular, the IVCwas fully occluded for approximately 30 seconds during which the bothleft ventricular end diastolic pressure (corresponding to lowerright-hand corner of the hysteresis loop) and left ventricular systolicpressure (corresponding to upper left-hand corner of the hysteresisloop) decreased during each successive heartbeat. LV pressure rapidlyincreased to pre-occlusion levels once the IVC occlusion was removed(i.e., similar to first half of the pressure and volume trace). BecauseIVC occlusion therapy proposed by Cedeno reduces systolic pressure, thetherapy can lead to reduced ejection fraction during systole, withpotentially dangerous consequences to the patient. In addition,occlusion of the IVC may result in congestion of the renal and hepaticveins, which could give rise to and exacerbate, rather than ameliorate,complications often associated with congestive heart failure.

Referring to FIG. 12 , changes in the LV pressure and LV volume areshown for a number of successive heart beats in a swine model followingpartial occlusion of the superior vena cava (SVC), as described inaccordance with the principles of the present invention. In particular,the SVC was partially occluded for approximately 30 seconds during whichthe left ventricular end diastolic pressure (corresponding to lowerright-hand corner of the hysteresis loop) decreased while the leftventricular systolic pressure (corresponding to upper left-hand cornerof the hysteresis loop) remained substantially unchanged during eachsuccessive heartbeat. LV pressure rapidly increased to pre-occlusionlevels once the SVC occlusion was removed (i.e., similar to first halfof the pressure and volume trace). Advantageously, the method of thepresent invention of partially occluding the SVC appears to have littleor no impact on ejection fraction during systole, but reduces wallstress in the ventricles during diastole. Moreover, as discussed in moredetail below, occlusion of the SVC will be tolerated well by thepatient, will not contribute to congestion of the renal or hepaticveins, and will not exacerbate complications often associated withcongestive heart failure including liver and kidney failure.

FIGS. 13-14 are graphs showing the changes in pressure as a function ofleft and right ventricular volume, respectively, during occlusion of thesuperior vena cava (SVC) and release in a swine treated for heartfailure in accordance with the principles of the present invention. Asshown in the graphs, SVC occlusion led to a significant reduction inleft ventricular (LV) volume (240 to 220 mL) and a reduction in LVdiastolic pressure (25 to 10 mmHg). SVC occlusion also was associatedwith reduction in LV systolic pressure (94 to 90 mmHg). SVC occlusionalso decreased right ventricular (RV) volume (230 to 210 mL), diastolicpressure (12 to 4 mmHg), and RV systolic pressure (27 to 16 mmHg).Advantageously, SVC occlusion in accordance with the systems and methodsdescribed herein reduces biventricular volume and diastolic (filling)pressures without negatively impacting systemic blood pressure (LVsystolic pressure). These findings suggest that SVC occlusion has apotentially important beneficial effect on biventricular interactionsuch that reducing diastolic filling pressures in both ventricles allowsfor increased ventricular compliance, thereby improving ventricularfilling and resulting in increased stroke volume and cardiac output,which is the primary objective when treating a patient with heartfailure.

FIG. 15 includes graphs showing that superior vena cava (SVC) occlusionin accordance with the principles of the present invention on a swinesubject improves cardiac function. The graphs each show the results forpartial inferior vena cava (IVC) occlusion (left side of each graph)versus full SVC occlusion (right side of each graph). The graphs showmeasured left ventricle (LV) stroke volume, cardiac output, LVcontractility, LV diastolic pressure, LV systolic pressure, andend-systolic volume.

FIG. 16 is graph showing that SVC occlusion in accordance with theprinciples of the present invention on three swine subjects does notharm systolic blood pressure. The graph shows the full caval occlusion(1 minute) LV end systolic pressure (mmHg) for full IVC occlusion (leftside of each study) versus full SVC occlusion (right column of eachstudy). Less reduction in LV-end-systolic pressure with SVC occlusioncompared to IVC occlusion.

FIG. 17 is graph showing that SVC occlusion in accordance with theprinciples of the present invention on three swine subjects does notharm LV diastolic filling. The graph shows the full caval occlusion (1minute) LV end diastolic pressure (mmHg) for full IVC occlusion (leftside of each study) versus full SVC occlusion (right side of eachstudy). Less reduction in LV-end-diastolic pressure with SVC occlusioncompared to IVC occlusion.

FIG. 18 is graph showing that SVC occlusion in accordance with theprinciples of the present invention on three swine subjects improves LVstroke volume. The graph shows the full caval occlusion (1 minute) LVstroke volume (mL/beat) for full IVC occlusion (left side of each study)versus full SVC occlusion (right side of each study). Increased LVstroke volume with SVC occlusion compared to reduced LV stroke volumeIVC occlusion.

FIG. 19 is graph showing that SVC occlusion in accordance with theprinciples of the present invention on three swine subjects improves LVcontractility. The graph shows the full caval occlusion (1 minute) LVcontractility (mmHg/sec) for full IVC occlusion (left side of eachstudy) versus full SVC occlusion (right side of each study). IncreasedLV contractility with SVC occlusion compared to reduced LV contractilitywith IVC occlusion.

FIG. 20 is four graphs depicting LV total volume and LV pressure for IVCocclusion (upper left), RV total volume and RV pressure for IVCocclusion (upper right), LV total volume and LV pressure for SVCocclusion (lower left), and RV total volume and RV pressure for SVCocclusion (lower right). FIG. 20 illustrates that SVC occlusion providesa significant reduction in LV and RV diastolic pressures without a majorreduction in LV systolic pressure as compared to IVC occlusion.

FIG. 21 includes two graphs depicting measured pulmonary artery pressureand renal vein pressure in a swine subject for IVC occlusion (leftgraph) and SVC occlusion (right graph). Line 100 shows the measuredpulmonary artery pressure while line 102 shows the measured renal veinpressure for IVC occlusion. Line 104 shows the measured pulmonary arterypressure while line 106 shows the measured renal vein pressure for SVCocclusion. The max renal vein pressure is measured to be 22 mmHg for IVCocclusion whereas the max renal vein pressure is measured to be 7 mmHgfor SVC occlusion. FIG. 21 demonstrates that SVC occlusion reducespulmonary artery pressures without increasing renal vein pressure ascompared to IVC occlusion.

FIG. 22 is a graph depicting measured left subclavian vein pressure andrenal vein pressure in a swine subjected to SVC occlusion in accordancewith the principles of the present invention. Line 108 shows themeasured left subclavian vein pressure while line 110 shows the measuredrenal vein pressure for SVC occlusion. The measured change in leftsubclavian vein pressure is 5 to 12 mmHg during SVC occlusion. FIG. 22demonstrates that proximal left subclavian vein pressure increasesnominally during SVC occlusion.

Results of additional animal testing conducted on swine models overvarious occlusion periods are shown in FIGS. 23A-26C. Referring now toFIGS. 23A to 23D, clinical pressure changes in left ventricular enddiastolic pressure, left ventricular end systolic pressure, leftventricular volume and ventricular stroke work, respectively, during thedeflation time of a one-minute episode of continuous SVC occlusion in apig model are depicted. Specifically, the controller was programmed tocause the flow limiting element to at least partially occlude the SVCfor one minute, and then contract, e.g., deflate, for one second. Asshown in FIGS. 23A to 23D, one-minute SVC occlusion may not besufficient to result in a steady-state reduction in ventricular volumesafter the deflation time.

Referring now to FIGS. 24A to 24D, clinical pressure changes in leftventricular end diastolic pressure, left ventricular end systolicpressure, left ventricular volume and ventricular stroke work,respectively, during the deflation time of a five minute episode ofcontinuous SVC occlusion in a pig model are depicted. Specifically, thecontroller was programmed to cause the flow limiting element to at leastpartially occlude the SVC for five minutes, and then contract, e.g.,deflate, for one second. As shown in FIGS. 24A to 24D, ventricularvolumes reached a clear steady-state reduction after the deflation timeas a result of five-minute SVC occlusion.

Referring now to FIGS. 25A to 25D, clinical pressure changes in leftventricular end diastolic pressure, left ventricular end systolicpressure, left ventricular volume and ventricular stroke work,respectively, during the deflation time of a ten minute episode ofcontinuous SVC occlusion in a pig model are depicted. Specifically, thecontroller was programmed to cause the flow limiting element to at leastpartially occlude the SVC for ten minutes, and then contract, e.g.,deflate, for one second. By a comparison of FIGS. 25A to 25D with FIGS.24A to 24D, the advantage of ten-minute SVC occlusion over five-minuteSVC occlusion is not significant in this model. Accordingly, inconsideration of patient safety, five-minute SVC occlusion was usedduring initial clinical studies such as the Tufts IRB-approved protocoldescribed below with reference to FIGS. 26A to 26C, though ten-minuteocclusion in a human subject is described in more detail below withrespect to FIGS. 28A-B.

Encouraged by animal testing, Applicants conducted preliminary humantesting and observed that a system constructed and operated inaccordance with the methods of the present SVC occlusion system providessignificant benefits. FIGS. 26A to 26C depict clinical pressure changesobserved during a five-minute episode of continuous SVC occlusion forthree human patients enrolled in a Tufts IRB-approved protocol.Specifically, the three patients underwent five minutes of continuousSVC occlusion with acute neuro and cardiac monitoring and thirty-dayneuro assessment (Table 1).

TABLE 1 Baseline Parameters Baseline Parameters Patient # 1 Patient # 2Patient # 3 Mean Right Atrial 30 21 18 Pressure Mean Pulmonary 52 44 28Artery Pressure Pulmonary Capillary 50 20 23 Wedge Pressure PCPW − RAP20 −1 5 Pressure Difference LV Ejection Fraction 10-15% 35% 25% SystolicPressure 130 128 135 Diastolic Pressure 97 72 84 Mean Arterial 108 90100 Pressure Cardiac Output 2.6 4.4 3.9 Heart Rate 73 83 60 NYHA Class 44 2 Overload Status severe severe moderate

As may be observed from FIGS. 26A to 26C and in Table 1, pulmonarycapillary wedge pressure (PCWP), pulmonary artery pressure, and rightatrial pressure changed significantly during the five minute episode ofSVC occlusion, and had residual effect after release of the balloon. Asa result of the study, all patients benefitted hemodynamically as therewas a drop in all filling pressures, e.g., capillary wedge pressure(CWP) and mean pulmonary artery (PA) pressure. It was observed that themore congested patients experienced an increase in mean arterialpressure (MAP). The net effect of these hemodynamic changes is areduction in cardio-pulmonary pressures and an increase in systemicpressures perfusing vital organs including the kidneys.

Encouraged by the foregoing preliminary swine and human results,Applicants performed additional testing on the three patients that werethe subject of the testing discussed above with respect to FIGS. 26A-26Cin addition to two new patients. The five human patients, each withheart failure, were subjected to the SVC occlusion system describedabove. Specifically, the five patients underwent five minutes ofcontinuous SVC occlusion. The baseline parameters of the five patientsare shown in Table 2 below. The third patient's New York HeartAssociation (NYHA) functional classification of 2 was the lowest. Theresults of the third patient suggest that application of the SVCocclusion system may preferably be used in patients with a NYHAfunctional classification of heart failure at level 3 and above.

TABLE 2 Baseline Parameters Baseline Parameters Pt #1 Pt #2 Pt #3 Pt#4Pt#5 Mean Right Atrial 30 21 18 12 22 Pressure Mean Pulmonary 52 44 2852 35 Artery Pressure Pulmonary Capillary 50 20 23 29 29 Wedge PressurePCWP − RAP 20 −1  5 17 7 Pressure Differential LV Ejection Fraction10-15% 35% 25% 20-25% 20% Systolic Pressure 130 128 135  124 164Diastolic Pressure 97 72 84 79 111 Mean Arterial 108 90 100  94 128Pressure Cardiac Output 2.6 4.4   3.9 4.2 6.4 Heart Rate 73 83 60 92 89NYHA Class 4 4   2 * 3 3 Overload status severe severe moderate not notknown known

FIGS. 27A-27E illustrates the change in systolic pressure (SP),diastolic pressure (DP), mean arterial pressure (MAP), mean pulmonaryartery (MPA) pressure, and pulmonary capillary wedge pressure (PCWP)from a baseline measurement for each of the five patients during andafter occlusion. In FIGS. 27A-27D, the change in systolic pressure (SP),diastolic pressure (DP), mean arterial pressure (MAP), and meanpulmonary artery (MPA) pressure is shown every minute during the fiveminutes of occlusion. In FIG. 27E, the change in pulmonary capillarywedge pressure (PCWP) is shown at five minutes of occlusion and afterocclusion.

The change in systolic pressure is illustrated in FIG. 27A. As is shownin FIG. 27A, the first, second and fifth patients generally experiencedan increase in SP during occlusion, while the third and fourth patientsgenerally experienced a decrease in systolic pressure. The change indiastolic pressure is illustrated in FIG. 27B. As is shown in FIG. 27B,the diastolic pressures during SVC occlusion generally increased forpatients one, two and five and generally decreased for patients threeand four.

The change in mean arterial pressure is illustrated in FIG. 27C. As isshown in FIG. 27C, the mean arterial pressure generally increased duringSVC occlusion for patients one, two and five, and generally decreasedfor patients three and four. The change in mean pulmonary arterypressure is illustrated in FIG. 27D. As is shown in FIG. 27D, the meanpulmonary artery pressure decreased during SVC occlusion for eachpatient, though it should be noted that the there is no data point forthe fourth patient at the fourth minute. The change in pulmonarycapillary wedge pressure (PCWP) is illustrated in FIG. 27E at fiveminutes and after release. As is shown in FIG. 27E, the pulmonarycapillary wedge pressure decreased for all patients at five minutes ofSVC occlusion, indicating a drop-in filling pressures for each patientduring occlusion.

As was observed in the study discussed with respect to FIGS. 26A-26C,the study illustrated in FIGS. 27A-27E indicated that all five patientsbenefitted hemodynamically as there was a drop in filling pressures,e.g., capillary wedge pressure (CWP) and mean pulmonary artery (PA)pressure and further, like the study discussed above with respect toFIGS. 26A-26C, the more congested patients generally experienced anincrease in mean arterial pressure (MAP). Also, in many cases, at leastsome of the patients had residual effects after release of the occluder.

Referring now to FIGS. 28A-28B, similar to the study discussed abovewith respect to FIGS. 25A-25D, Applicants also studied the effect ofprolonged SVC occlusion on a human subject. Specifically, the controllerwas programmed to cause the SVC flow limiting element to at leastpartially occlude the SVC for ten minutes. Prior to the ten-minuteocclusion, the SVC was occluded for a period of five minutes and thenpermitted to rest for a period of five minutes. The change in meanpulmonary artery pressure, and the change in mean arterial arterypressure, from a baseline measurement before occlusion (i.e., after fiveminutes of rest), was measured at each minute from 1-10 minutes ofocclusion, and after release. As is shown in FIGS. 28A-B, the effectsobserved during five minutes of occlusion persisted throughout theten-minute occlusion period without any attrition of the‘cardio-pulmonary unloading’ effect.

FIG. 28A illustrates the change in mean pulmonary artery pressure. As isshown in FIG. 28A, the mean pulmonary artery pressure decreasedthroughout the entirety of the occlusion and even reached its lowestlevel during the final two minutes of occlusion. FIG. 28B illustratesthe change in mean arterial pressure change during occlusion. As isshown in FIG. 28B, the mean arterial pressure generally decreased duringocclusion though it fluctuated, rising above the baseline measurement atthe first minute and then again at the fourth and fifth minutes.

Referring now to FIG. 29 , Applicants also performed more extensivetesting involving use of the system and methods of the present inventionover successive periods of occlusion resulting in arresting or reversingfurther myocardial remodeling and degeneration. Specifically, adult maleswine were subjected to a heart attack by occluding the left anteriordescending artery (LAD) for 120 minutes, followed by a re-opening of theblocked artery. Repetitive cycles of SVC occlusion were then performed,occluding the SVC for 5 minutes and deflating the occlusion device for30 minutes. The repetitive cycles were repeated and performed for 18hours. After each cycle of SVC occlusion, cardiac output was measured.FIG. 29 illustrates the results of the repetitive cycles of SVCocclusion.

As is shown in FIG. 29 , cardiac output was at its lowest point post-LADinfarct but before SVC occlusion treatment. After one hour of treatment,cardiac output had returned to baseline levels. Cardiac output continuedto gradually increase from one hour of treatment to eighteen hours oftreatment, reaching a maximum cardiac output at eighteen hours. Thesefindings suggest for the first time that after acute heart injury,mechanically reducing cardiac pressure and volume (i.e., unloading) byintermittently occluding the SVC and thereafter ceasing occlusion (i.e.,recovery) may condition the heart muscle, allowing for periods ofexercise and rest. In this manner, the repetitive cycles are akin tointerval-training high-intensity workouts (e.g., sprinting) followed byrest. The repetitive cycles strengthen the heart and improve cardiacoutput and function. While the ratio of occlusion-to-rest was 10:1 (5minutes on, 30 seconds off), it is understood that other ratios wouldproduce beneficial results. For example, a ratio range of 5-20 minutesof occlusion to 10-100 seconds of rest may be beneficial. It is furtherunderstood that occluding the SVC for up to 95% of an hour may bebeneficial. Accordingly, the SVC occlusion system described herein mayalternatively or additionally be used post-infarction to treat injuriesto the heart from the infarction to enhance recovery through myocardialunloading.

As referenced above, the SVC occlusion system described herein mayalternatively or additionally be used to treat pulmonary hypertension asocclusion of the SVC may result in reduced pressure in the pulmonaryarteries. While heart failure is a common cause of pulmonaryhypertension, pulmonary hypertension may be caused by primary lungdisease. It is understood that the SVC occlusion system may be used totreat pulmonary hypertension, whether or not the cause of pulmonaryhypertension is heart failure.

Referring now to FIG. 30 , Applicants have observed that implantation ofthe SVC occlusion system in five patients with pulmonary hypertensiondue to heart failure results in significant reduction in the pulmonaryartery systolic pressure (PASP). The patients were subject to fiveminutes of SVC occlusion, mechanically reducing cardiac pressure andvolume (i.e., unloading). As is shown in FIG. 30 , SVC occlusionsignificantly reduced the PASP below the level of moderate pulmonaryhypertension, defined as elevated PASP above 50 mmHg. Accordingly, theSVC occlusion system described herein may implanted to treat pulmonaryhypertension. As discussed above with respect to FIG. 26B as well asFIG. 27D, Applicants also observed that implantation of the SVCocclusion system resulted in a decrease in the mean pulmonary arterypressure for each patient.

The benefits observed in the foregoing animal and human testing suggeststhat successive SVC occlusion could be used to treat any heart injuryincluding, but not limited to, acute heart injury due to a heart attack,myocarditis, valvular insufficiency, volume overload or congestive heartfailure, and many other acute or chronic heart injury. In one example,the SVC occlusion system described herein may be used acutely, e.g., inan acute-care setting, to arrest or reverse the systems of heartfailure, thereby shifting the Frank-Starling curve illustrated in FIG.2A, toward line 7 representing a healthy patient. In this manner, thepatient will see immediate improvement in increased cardiac performance,with further continuous improvement in myocardial function throughoutthe course of treatment. To prolong the effects of the system, the SVCocclusion system may be implanted within the patient for long term use.As the SVC occlusion system described herein may be implanted or worn bythe patient continuously and in an ambulatory setting, rather than beingconfined to a bed, the patient may receive the benefits of the systemover a much longer period as compared to acute care.

FIG. 31 is a prophetic example of how SVC occlusion in accordance withthe principles of the present invention is expected to change over thecourse of the disease. For example, primary benefits include betterpatient hemodynamics, faster recovery, and decreased length of stay(LOS) of patients in the hospital. Over time, SVC occlusion maysignificantly slow disease progression.

Referring now to FIG. 32 an alternative flow limiting element isillustrated. One undesired effect of occlusion of the SVC is increasedvenous blood pressure upstream of the occlusion device. It is well knownthat high cephalic venous pressure may lead to various unwanted effects.To reduce this risk of excessive pressure buildup upstream of the flowlimiting element, a relief valve may be integrated into a flow limitingelement, as illustrated in FIG. 33 , to permit fluid flow from the SVCto the right atrium. The relief valve may be unidirectional, permittingblood flow only in the direction of the right atrium. The relief valveis preferably configured to open at a pressure in the SVC between 30-60mmHg. However, it is understood that the relief valve may be designedand configured to open at other pressures in the SVC.

The flow limiting element illustrated in FIG. 32 may be used with asystem similar to the system illustrated in FIGS. 4A-4B. As is shown inFIG. 32 , the flow limiting element may be cylindrical flow limitingelement 112. Cylindrical flow limiting element 112 may includecylindrical balloon 113 which may be inflated and deflated by deliveringfluid to cylindrical balloon 113 from a catheter. Flow limiting element112 may be sized and configured to fit within the SVC and may conform tothe contours of the inner wall of the SVC. Flow limiting element 112 maybe delivered to the SVC on a catheter. Cylindrical balloon 113 may beintroduced to the SVC in a deflated configuration. Upon arriving at theSVC, cylindrical balloon 113 may be inflated to obstruct or limit bloodflow in the SVC.

Cylindrical balloon 113 may define internal lumen 114 when cylindricalballoon 113 is inflated. When relief valve 115 is open and cylindricalballoon 113 is inflated, blood may pass through cylindrical balloon 113.Internal lumen 114 may extend from one end of cylindrical balloon 113 tothe other. While internal lumen 114 may have a consistent cylindricalshape throughout, it is understood that the size and shape of bothcylindrical balloon 113 and internal lumen 114 may vary. Additionally,internal lumen 114 need not be aligned with the center of the balloonand may even adopt a non-cylindrical shape.

Referring now to FIG. 33 , a cutaway view of cylindrical flow limitingelement 112 is shown. As is shown in FIG. 33 , relief valve 115 may becoupled to the internal wall of cylindrical balloon 113 within centrallumen 114. Relief valve 115 may include a single flow obstructingelement or a plurality of flow obstructing elements (e.g., a pluralityof flexible leaflets) that work in concert to obstruct blood flowthrough central lumen 114. Relief valve 115 may be coupled to the centerof cylindrical flow limiting element 112 or alternatively may bepositioned closer to or at an upstream or downstream end of cylindricalflow limiting element 112. For example, relief valve 115 may bepositioned at an upstream end of cylindrical flow limiting element 112furthest from the right atrium of the patient. This configuration mayavoid pooling of blood or a standing column of blood within centrallumen 114 which may occur where relief valve 115 is positioned in acentral or downstream region of central lumen 114.

Relief valve 115, illustrated in FIG. 33 in a closed position, may bedesigned to open at a certain pressure. For example, relief valve 115may be designed to open at a pressure between 30-40 mmHg. However, it isunderstood that other pressures may also be desirable. Below thepressure at which relief valve 15 is designed to open, relief valve 115may obstruct fluid flow through central lumen 114. Above the pressure atwhich relief valve 115 is designed to open, relief valve 115 may permitthe passage of blood through internal lumen 114, thereby reducingcephalic venous pressure.

Relief valve 115 may be constructed of any suitable biocompatiblematerial, including, but not limited to, elastomers, rigid or flexiblepolymers, metals, and any combination thereof. The functionality of therelief valve 115 may depend solely on the materials and design (i.e.,elasticity, rigidity, thickness) of the valve, and/or may be dictated bymechanical, electrical, and/or magnetic features. The threshold forwhich the valve permits fluid to flow may be predetermined by valvedesign and/or may be mechanically adjustable.

Referring now to FIGS. 34A and 34B, two different relief valve designsare shown within internal lumen 114 of cylindrical flow limiting element112. Binary relief valve 116, shown in FIG. 34A, maintains asubstantially closed position until rapidly transitioning to asubstantially open position when a given force is applied. The force atwhich relief valve 116 transitions from a closed to an open position ispreferably between 30-60 mmHg though it is understood that this pressurecould be any pressure. To achieve the binary (i.e., on/off)functionality, binary relief valve may include a cutout section designedto give-way in response to a given force. Upon opening and permittingfluid to pass, thereby releasing pressure, elasticity in the material orother mechanical features may cause binary relief valve 116 to springback into a closed position. It is understood that this binaryfunctionality may be achieved using a variety of other designs and/or byincorporating other materials. For example, relief valve 132 in FIG.38A-B may also achieve the binary functionality.

Gradual relief valve 117, as shown in FIG. 34B, is designed to opengradually with increasing pressure. This functionality may be achieved,for example, with valve leaflets that have a constant thickness or aprogressively thinner cross-section as the leaflets move from theinternal wall of cylindrical balloon 113 towards the center of internallumen 114. However it is understood that any valve design that graduallypermits increased fluid flow in response to increased pressure may beused as a gradual relief valve.

Referring now to FIG. 35 , a top view of cylindrical flow limitingelement 112 is shown. Relief valve 115, shown here in a closed position,prevents flow through the internal lumen of cylindrical balloon 113 aslong as pressure remains below a certain threshold. Although a reliefvalve design having four flexible leaflets or flaps is depicted, anyrelief valve design that may be coupled within internal lumen 114 ofcylindrical balloon 113 may be used including valves with fewer/moreleaflets.

Referring now to FIGS. 36A and 36B, a top view of cylindrical flowlimiting element 112 is shown. FIG. 36A illustrates binary relief valve116, also shown in FIG. 34A, in its open position. FIG. 36B illustratesgradual relief valve 117, also shown in FIG. 34B, in a partially openposition. As discussed above, binary relief valve 116 is designed toopen to a substantially open position upon reaching its set pressure. Onthe other hand, gradual relief valve 117 is designed to open graduallyas pressure increases above a certain threshold.

Referring now to FIGS. 37A and 37B, it may be desirable to place a stent118 around cylindrical balloon 113. Stent 118 may, for example, serve asboth a receiver and emitter of electrical signals. Such uses include,but are not limited to, serving as an ECG lead, emitting signals relatedto autonomic activity, and receiving neuromodulation signals. Stent 118may be self-expanding and may be made of an electrically conductivematerial. Stent 118 may be integrated into to cylindrical flow limitingelement 112 and/or may be removably coupled to cylindrical flow limitingelement 112.

Referring now to FIGS. 38A and 38B, cylindrical flow limiting element130 is illustrated. As is shown in these figures, cylindrical flowlimiting element 130 includes balloon occluder 131 and relief valve 132which are both integrated into stent 118. Relief valve 132 and balloonoccluder 131 are located adjacent to each other within stent 118. FIG.38A depicts the cylindrical flow limiting element 130 in its inflatedposition, occluding flow within the SVC. FIG. 38B depicts the occlusiondevice in its deflated position, permitting flow through the SVC. As isillustrated in FIG. 38B, balloon occluder 131 may be coupled to reliefvalve 132 and when deflated may contract toward relief valve 132. Reliefvalve 132 may be hinged to stent 118 and may open to permit blood flowwhen a certain pressure is achieved within the SVC. Relief valve 132 maybe constructed using any of the techniques, designs, and materialsdisclosed above with respect to relief valves.

Referring now to FIGS. 39A and 39B, cylindrical flow limiting element133 is illustrated. As is shown in these figures, cylindrical flowlimiting element 133 includes cylindrical balloon occluder 134 andrelief valve 135 which are both integrated into stent 118. Cylindricalballoon occluder 134 may be inflated to conform to the shape of stent118. As is shown in FIG. 39B, cylindrical balloon occluder 134 may havean outer surface that is coupled to stent 118 along a portion of theouter surface. Relief valve 135 may be coupled to cylindrical balloonoccluder 134. Cylindrical balloon occluder 134 may define internal lumen136 when inflated through which blood may pass if relief valve 135 isopen.

FIG. 39A depicts cylindrical flow limiting element 133 with cylindricalballoon occluder 134 in an inflated configuration. When inflated,cylindrical balloon occluder 134 limits flow within the SVC. Withcylindrical balloon occluder 134 inflated, relief valve 135 may open asrequired to relieve any overpressure in the SVC. FIG. 39B depictscylindrical flow limiting element 133 in a deflated configuration. Whendeflated, cylindrical flow limiting element 133 permits flow through theSVC. In the deflated configuration, cylindrical balloon occluder 134reduces in size and moves toward the portion of the stent wall thatcylindrical balloon occluder 134 is coupled to. Similarly, relief valve135 moves toward stent 118 when cylindrical flow limiting element 133 isin a deflated configuration. Cylindrical balloon occluder 134 having areduced size when deflated, permits blood to flow through stent 118,around deflated balloon occluder 134.

Referring now to FIGS. 40A and 40B, cylindrical flow limiting element137 is illustrated. Cylindrical flow limiting element 137 includes stent118 and relief valve 138. Unlike the occlusion devices illustrated inFIGS. 32-39 , cylindrical flow limiting element 137 does not include aballoon. Instead, relief valve 138 may be coupled directly to stent 118as is shown in FIG. 40B. Stent 118 may be an expandable stent and may beanchored to the inner wall of the SVC. Relief valve 138 may take theform and have characteristics similar to any of the relief valvesdiscussed above with respect to FIGS. 32-39 . Cylindrical flow limitingelement 137 may entirely eliminate flow in the SVC until a certainthreshold pressure his achieved in the SVC, at which point relief valve138 may open to permit flow from the SVC to the right atrium.

Referring now to FIG. 41 , cylindrical flow limiting element 112 of FIG.32 is illustrated coupled to filter 126. Filter 126 may be placeddownstream of cylindrical flow limiting element 112. When relief valve115 is closed, blood may pool in central lumen 114 of cylindricalballoon 113 resulting in a stagnant blood column, leading to thrombosis.When relief valve 115 is opened, thrombus may be released into the rightatrium, which may cause severe problems and even death. Filter 126, maybe supported either directly by a catheter or by a structural feature ofcylindrical flow limiting element 112 such as cylindrical balloon 113,relief valve 115, or stent 118 if applicable, and may serve to catchthrombus. For example, filter 126 may be coupled to cylindrical balloon113 at the downstream end of cylindrical flow limiting element 112, asis shown in FIG. 41 . It is understood that filter 126 may be integratedinto any of the flow limiting elements described herein.

To determine whether the SVC is fully occluded or to what degree the SVCis occluded, traditional methods involving injecting contrast agent intothe patient and observing movement of the contrast agent underfluoroscopy may be employed. Alternatively, pressure sensors may bepositioned relative to the occlusion balloon as discussed herein, andpressure waveforms may be analyzed to determine whether the SVC isoccluded. For example, CardioMEMS™ HF System pressure sensors areavailable from Abbott, St. Paul, Minn. The pressure sensors maycommunicate wirelessly with, e.g., the implanted controller. Pressurewaveforms may also be analyzed to determine a patient's fillingpressures, diastolic conditions and/or other cardiac conditions orindications. For example, waveforms may be analyzed to detect aprominent ‘C-V’ wave indicative of tricuspid regurgitation due to volumeoverload. In another example, waveforms may detect an ‘A’ wavesuggestive of complete heart block, Ventricular Tachycardia (VT), orpulmonary hypertension. The systems described herein may be used as adiagnostic monitoring tool by analyzing waveforms and may respondaccordingly using the SVC occlusion techniques described herein.

FIG. 42A illustrates pressure sensor 140 which may generate pressurewaveforms. Pressure sensor 140 may be incorporated into catheter 31 andmay be disposed at a location proximal to the occlusion balloon toprovide pressure measurements indicative of the Jugular Vein Pressure(JVP). Pressure sensor 156 optionally may be incorporated into catheter31 distal to the occlusion balloon. A user of the system illustrated inFIG. 42A may monitor the waveform readings from pressure sensor 140 anddetermine when the wave form changes from phasic to non-phasic. When theocclusion balloon is deflated, the pressure waveform will vary in phasewith the heartbeat, as is illustrated in curve 141 of FIG. 42B. When theocclusion balloon is inflated, the pressure waveform then flatlines. Inthis manner it may be determined whether the SVC is occluded, withoutthe need to inject contrast and without the patient being in a cathlabor under x-ray. Also, the pressure waveform may be used to determinewhen to actuate the flow limiting element and when to cease actuation ofthe flow limiting element.

Another alternative to using x-ray/fluoroscopy for determining occlusionof the SVC employs two pressure sensors on opposite sides of theoccluding device. For example, FIG. 4A discussed above illustrates asystem having catheter 31 including flow limiting element 32, sensor 42and sensor 43. As is shown in FIG. 4A, sensor 42 is positioned distal toflow limiting element 32 and sensor 43 is positioned proximal to flowlimiting element 32. Sensors 42 and 43 may be pressure sensors and, asexplained above, may be used to determine the extent of occlusion causedby flow limiting element 32, for example, by monitoring the pressuredifferential across flow limiting element 32. The pressure differentialvalue may be indicative of the amount or degree of occlusion. Also thepressure differential may be used to determine when to actuate the flowlimiting element and when to cease actuation of the flow limitingelement.

While FIG. 4A illustrates one arrangement of sensors, it is understoodother arrangements of sensors may be used to obtain relevantinformation. As shown in FIG. 43 , an alternative sensor arrangementincludes catheter 31, which may be introduced into the vasculature ofthe patient via a delivery device, such as introducer sheath 144.Catheter 31 preferably extends into the SVC, enters the heart throughthe right atrium, extends into the right ventricle, and enters thepulmonary artery through the pulmonary valve. Sensors 145, 146 and 147may be positioned along catheter 31 so that sensor 145 is positionedwithin flow limiting element 32 to measure the pressure within flowlimiting element 32 (i.e., balloon pressure), sensor 146 is positionedalong catheter 31 distal to flow limiting element 32 and within the SVCto measure SVC or right atrium pressure, and sensor 147 is positionedalong catheter 31, distal to sensor 146, such that sensor 147 ispositioned within the pulmonary artery and measures pulmonary arterypressure. To measure the pressure above or proximal to flow limitingelement 32, sensor 148 may be placed directly on or otherwiseincorporated into the distal end of sheath 144, where introducer sheath144 enters the SVC. The pressure measured by sensor 148 is indicative ofthe JVP. Catheter 31 may include a plurality of lumens, which are usedas inflation lumens, actuation lumens and/or for electricalcommunication between the controller and flow limiting element 32 and/orsensors 145, 146 and 147. Introducer sheath 144 also may include lumensfor electrical communication between sensor 148 and the controller.

Referring now to FIG. 44 , yet another alternative embodiment isdescribed that includes introducer sheath 144. The embodimentillustrated in FIG. 44 is similar to that of FIG. 43 except that flowlimiting element 32 and sensor 145 and 146 are also incorporated intointroducer sheath 144. Similar to the device illustrated in FIG. 43 ,sensor 148 may be positioned above or proximal to flow limiting element32 and may measure pressure above or proximal to flow limiting element32, which is indicative of JVP. Sensor 145 is positioned within flowlimiting element 32 to measure the pressure within flow limiting element32 (i.e., balloon pressure). Sensor 146 is positioned near a distal endof introducer sheath 144, which is distal to flow limiting element 32and positioned within the SVC to measure SVC or right atrium pressure.Also, similar to the device illustrated in FIG. 43 , catheter 31 may beintroduced via introducer sheath 144 and extend through the right atriumand into the pulmonary artery. Sensor 147 preferably is disposed at adistal end of catheter 31 so that it is positioned within the pulmonaryartery and measures pulmonary artery pressure. Introducer sheath 144 mayinclude a plurality of lumens used as inflation lumens, actuation lumensand/or for electrical communication between the controller and flowlimiting element 32 and/or sensors 145, 146 and 148. Catheter 31 mayalso include lumens for electrical communication between sensor 147 andthe controller.

In the embodiment of FIG. 44 , flow limiting element 32 may beselectively inflated and deflated independent of the presence ofcatheter 31. As flow limiting element 32 and sensors 145, 146 and 148are disposed on introducer sheath 144, therapeutic treatment involvingthe inflation and deflation of flow limiting element 32 to selectivelyocclude the SVC may be achieved without the introduction of catheter 31.Further, pressure differentials across flow limiting element 32 may bedetermined using sensors 148 and 146 whether or not catheter 31 isdeployed.

Referring now to FIG. 45 , yet another embodiment of the SVC occlusionsystem constructed in accordance with the principles of the presentinvention is described. Catheter 31 preferably includes two occlusionballoons, azygos vein occlusion balloon 142 and SVC occlusion balloon143. Sensors, 129, 139 and 149 may also be disposed on catheter 31 suchthat sensor 129 is disposed proximal to azygos vein occlusion balloon142 to measure pressure distal to azygos vein occlusion balloon 142,sensor 139 is disposed between azygos vein occlusion balloon 142 and SVCocclusion balloon 143 to measure the pressure between azygos veinocclusion balloon 142 and SVC occlusion balloon 143, and sensor 149 isdisposed distal to SVC occlusion balloon 143 to measure the pressuredistal to SVC occlusion balloon. Also, sensor 145 is positioned withinSVC occlusion balloon 143 to measure the pressure within SVC occlusionballoon 143 (i.e., SVC occlusion balloon pressure) and sensor 155 ispositioned within azygos vein occlusion balloon 142 to measure thepressure within azygos vein occlusion balloon 142 (i.e., azygos veinocclusion balloon pressure). Further, pressure differentials acrossazygos vein occlusion balloon 142 and SVC occlusion balloon 143 may bedetermined using sensors 129 and 139, and 139 and 149, respectively. Thepressure differential value may be indicative of the amount or degree ofocclusion.

Azygos vein 16 drains the posterior part of the thorax into the SVC.When the SVC is blocked, the azygos vein may provide an alternative pathto the right atrium, thereby naturally shunting occluded SVC blood flowback to the right atrium. Specifically, if the SVC is occluded below theorigin of the azygous vein, pressure built up above the occluded portionof the SVC may cause a percentage of venous blood to move retrogradethrough the azygous vein into the thorax. Azygos vein occlusion balloon142 may be positioned in the SVC adjacent the azygos vein such thatinflation of azygos vein occlusion balloon 142 restricts or preventsblood flow from entering the azygos vein from the SVC. SVC occlusionballoon 143 may be positioned below the azygos vein, distal to azygosvein occlusion balloon 142, such that inflation of SVC occlusion balloon143 occludes the SVC but permits blood flow into the azygos vein.Catheter 31 may include a plurality of lumens used as inflation lumensand/or actuation lumens between the controller and azygos vein occlusionballoon 142 and SVC occlusion balloon 143.

Azygos vein occlusion balloon 142 and SVC occlusion balloon 143 may beselectively and independently be inflated and deflated. For example,Azygos vein occlusion balloon 142 may be deflated while SVC occlusionballoon 143 may be inflated, Azygos vein occlusion balloon 142 may beinflated while SVC occlusion balloon 143 is deflated, or both balloonsmay be inflated or deflated at the same time. Azygos vein occlusionballoon 142 and SVC occlusion balloon 143 may also be fully or partiallyinflated depending upon how much flow back to the right atrium isdesirable.

When SVC occlusion balloon 143 is inflated and the azygos vein occlusionballoon 142 is deflated, the SVC is open above SVC occlusion balloon 143and blood is permitted to travel through the azygos vein to the rightatrium. Should it be desirable to further reduce flow back to the rightatrium (further reducing preload), azygos vein occlusion balloon 142 maybe inflated, thereby occluding the azygos vein and preventing it fromacting as a natural shunt.

The systems and methods of the present invention may be used alone, asdescribed in the examples above, or in combination with other devicesconfigured to assist cardiac function. For example, SVC occlusion inaccordance with the principles of the present invention may be used incombination with a pump such as an intra-aortic balloon pump (“IABP”) ora percutaneous or surgical left ventricular assist device (“LVAD”),right ventricular assist device (“RVAD”) or any other cardiovascular(i.e., heart, venous, arterial) pump, whether used for full cardiacsupport or for temporary assistance, thereby allowing for synchronous orasynchronous (venous and arterial) unloading of cardiac preload andafterload, respectively. For example, SVC occlusion in accordance withthe principles of the present invention may be used in combination withthe Impella® heart pump available from Abiomed®, Danvers, Mass., asdescribed in further detail below with reference to FIG. 49 . FIGS. 49and 51-54 illustrate the SVC occlusion system combined with exemplaryRVAD, LVAD, and IABP systems.

A system of the present invention also could be coupled to other devicessuch as biventricular pacemakers and neuromodulatory devices. Forexample, biventricular pacemakers are designed to resynchronize cardiacfunction; if SVC occlusion favorably alters RV and LV interaction, thenit may render biventricular pacing more efficient. Similarly, SVCocclusion therapy may be used in conjunction with neuromodulatorydevices such that the systems have significant combined action instimulating vagal efferents, thereby enhancing the efficacy of theneuromodulatory device. A further potential application may be inunmasking right ventricular failure after a patient is outfitted with anLVAD. By modulating the amount of venous return to the right ventricle,it may be possible to reduce overload and thereby “condition” the rightventricular myocardium to tolerate enhanced venous return being drivenby the LVAD.

While flow limiting element 32 is described above as being positionedwithin the SVC and inflated and deflated within the SVC, therapeuticocclusion of the SVC as described herein alternatively may be achievedusing a cuff wrapped around the exterior of the SVC to selectivelyconstrict the SVC. Referring now to FIG. 46 , cuff 150 is illustratedwrapped around the SVC. As further depicted in FIGS. 47A-D, cuff 150 mayinclude strap 151, occlusion element 152 and locking element 153.Occlusion element 152 may be incorporated into strap 151 such thatocclusion element 152 extends outward from both an exterior surface ofstrap 151 illustrated in FIG. 47A and an interior surface of strap 151,illustrated in FIG. 47B. The interior side or surface of strap 151 isthe side facing the SVC and the exterior side or surface of strap 151 isthe side facing away from the SVC.

Strap 151 may be generally rectangular in shape. Locking element 153 maybe any well-known system for removably affixing one side of strap 151 toanother side of strap 151. For example, strap 151 may have a magneticlocking element for tightly securing cuff 150 to the SVC. Air line 154may connect to occlusion element 152 on one end and a controller on theother end. Occlusion element preferably has elastic properties such thatit inflates when air line 154 delivers air or other fluid to occlusionelement 152. Occlusion element 152 may expand outwardly from theinterior side of strap 151 when inflated.

Referring again to FIG. 46 , strap 151 of cuff 150 may be wrapped aroundthe SVC and locked tightly onto the SVC using locking element 153. Uponlocking cuff 150 into place on the SVC, occlusion element 152 may beselectively inflated and thus expanded toward the SVC by deliveringfluid through air line 154. As strap 151 is substantially non-elastic,the inflation of occlusion element 152 will result in expansion ofocclusion element 152 and compression of the SVC, thereby restrictingflow through the SVC. Accordingly, occlusion of the SVC may be achievedwhen occlusion element 152 expands and encroaches into the SVC, causingthe SVC to collapse inward. Thus, by selectively deflecting andinflating occlusion element 152, therapeutic occlusion of the SVCdescribed herein may be achieved.

Controller 33 is programmed to cause flow limiting element 32 to atleast partially occlude the SVC for a first predetermined time interval,and then contract, e.g., deflate, for a second predetermined timeinterval, e.g., at least one second, less than one minute, or one tothirty seconds. Preferably, the first predetermined time interval ismore than a minute, between two and eight minutes, or between four andsix minutes. For example, the first predetermined time interval may befive minutes, plus or minus a minute. In addition, the firstpredetermined time interval is preferably significantly longer than thesecond predetermined time interval. For example, the first predeterminedtime interval may be at least 5 times longer, at least 10 times longer,at least 20 times longer, or at least 30 times longer than the secondpredetermined time interval. In some data described herein, for example,the occlusion time interval is 5 minutes while the contracted timeinterval is 10 seconds. In some embodiments, controller 33 is programmedto cause flow limiting element 32 to fully occlude the SVC during thefirst predetermined time intervals. Controller 33 may be programmed tocause flow limiting element 32 to transition from the occlusion statefor the first predetermined time interval to the contracted state forthe second predetermined time interval for many cycles throughout thecourse of a treatment. As further described herein, controller 33 may beprogrammed to cause flow limiting element 32 to adjust the timing of thefirst predetermined time interval (e.g., to a third predetermined timeinterval) and/or to adjust timing of the second predetermined timeinterval (e.g., to a fourth predetermined time interval) automatically(e.g., responsive to parameters sensed by a sensor(s)) and/or responsiveto user input. As will be understood by one skilled in the art, furtheradjustments to the time intervals may be made throughout the course ofthe treatment.

Referring now to FIG. 48 , an alternative exemplary system 30′ of thepresent invention is described. System 30′ is similar to system 30, andincludes catheter 31 having flow limiting element 32 disposed on distalportion 34. System 30′ differs from system 30 in that catheter 31 isremovably coupled at proximal end 35 to external controller system 200.For example, catheter 31 may be decoupled from controller 33 and coupledto external controller system 200 during a hospital visit so theclinician may monitor and adjust operation of flow limiting element 32directly. Catheter 31 may include optional distal flotation balloon 201disposed on distal portion 34, distal to flow limiting element 32. Asshown in FIG. 48 , distal flotation balloon 201 may be positioned withinthe pulmonary artery of the patient.

External controller system 200 includes display 202, e.g., graphicaluser interface, electrically coupled to inflation source 203 andexternal controller 204. Display 202 communicates with inflation source203 and external controller 204 to display information, e.g. vitalphysiologic or system parameters, regarding functioning of system 30′for review or adjustment by the clinician, or an alert generated byexternal controller 204. The clinician may review the data displayed ondisplay 202 to address a malfunction or to adjust the system parametersvia the graphical user interface.

Inflation source 203 includes a drive mechanism, e.g., motor, pump, foractuating flow limiting element 32. Inflation source 203 furtherincludes a source of inflation medium, e.g., gas or fluid, such that thedrive mechanism may transfer the inflation medium between inflationsource 203 and flow limiting element 32 via flow limiting elementconnector 209 responsive to commands from external controller 204. Inaddition, catheter 31, when partially external, provides a fail-safedesign, in that flow limiting element 32 only can be inflated to provideocclusion when the proximal end of catheter 31 is coupled to externalcontroller 204. Such a quick-disconnect coupling at proximal end 35permits the catheter to be rapidly disconnected from external controller204 for cleaning and/or emergency.

External controller 204 includes a processor programmed to controlsignals to the drive mechanism of inflation source 203, and memory forstoring instructions thereon. External controller 204 also includes apower supply, e.g., battery that provides the power needed to operatethe processor, inflation source 203, and display 202. Alternatively,external controller 204 may receive power via an electric cord pluggedinto a source of electric energy, e.g., an electric outlet.

Catheter 31 may be coupled at proximal end 35 to distal flotationballoon connector 205 for fluid communication with a source of inflationmedium, e.g., gas or fluid, such that an inflation medium may betransferred between the source of inflation medium and distal flotationballoon 201 responsive to commands from external controller 204, tothereby anchor distal flotation balloon 201 within the pulmonary arteryof the patient. Catheter 31 also may be coupled at proximal end 35 tothermistor connector 206 for communication with a cardiac output (CO)monitor for measuring and monitoring temperature, and to pulmonaryartery pressure connector 207 for communication with the CO monitor formeasuring and monitoring pulmonary artery pressure.

External controller 204 may be coupled to catheter 31 at proximal end 35via right atrial pressure connector 208 for measuring and monitoringright atrial pressure. External controller 204 also may be coupled tocatheter 31 at proximal end 35 via flow limiting element connector 209for measuring and monitoring the amount of inflation medium transferredbetween inflation source 203 and flow limiting element 32, e.g., thepressure within flow limiting element 32. External controller 204 alsomay be coupled to jugular vein pressure connector 210 for measuring andmonitoring jugular vein pressure coming from a sheath sideport.

The processor of external controller 204 may include a data transfercircuit as described above that monitors an input from an externalsensor, e.g., positioned on catheter 31, and provides that signal to theprocessor. The processor is programmed to receive the input from thedata transfer circuit and adjust the interval during which flow limitingelement 32 is maintained in the expanded state, or to adjust the degreeof occlusion caused by flow limiting element 32. Thus, for example,catheter 31 may have one or more optional sensors positioned withindistal portion 34 of the catheter to measure parameters, e.g., heartrate, blood flow rate, blood volume, pressure including cardiac fillingpressure and central venous pressure. The output of the sensors isrelayed to the data transfer circuit of external controller 204, whichmay pre-process the input signal, e.g., decimate and digitize the outputof the sensors, before it is supplied to the processor. The signalprovided to the processor allows for assessment of the effectiveness offlow limiting element 32, e.g., by showing reduced venous pressureduring occlusion and during patency, and may be used by the clinician todetermine how much occlusion is required to regulate venous blood returnbased on the severity of congestion in the patient. As will beunderstood by one or ordinary skill in the art, system 30′ may employany combination of flow limiting elements and sensors as describedabove.

Referring now to FIG. 49 an SVC occlusion system in combination with atrans-valvular LVAD is described. For example, SVC occlusion system 30having flow limiting element 32 at distal portion 34 of catheter 31 maybe positioned within the SVC, as described above, to at least partiallyocclude the SVC intermittently, and LVAD system 211 may be positioned inthe left side of the heart, offering full hemodynamic support. In oneexample, LVAD system 211 is an Impella CP® heart pump available fromAbiomed® of Danvers, Mass. LVAD system 211 illustratively includesinflow end 212, outflow end 213, impeller pump 214, and anchor 215,disposed on a distal portion of catheter 216. For example, anchor 215may be a pigtail anchor. During operation, inflow end 212 is positionedin the left ventricle and outflow end 213 is positioned in the ascendingaorta. As impeller pump 214 is actuated, blood within the left ventricleis pumped through inflow end 212 and expelled into the aorta via outflowend 213, thereby mimicking the natural pathway of blood flow, unloadingthe left ventricle, and increasing coronary and systemic perfusion. Forexample, impeller pump 214 may deliver up to 5.0 L/min of forward bloodflow from the left ventricle to the aorta. As will be understood by onehaving ordinary skill in the art, any suitable pump may be used.

In addition, LVAD system 211 includes controller 217 configured to beoperatively coupled to catheter 216 to actuate pump 214 to pump bloodfrom the left ventricle to the aorta, thereby unloading the leftventricle and increasing coronary and systemic perfusion. Controller 217and controller 33 may be the same and/or incorporated into the samehousing unit, such that a single controller is operatively coupled toflow limiting element 32 and pump 214. Controller 33 may actuate flowlimiting element 32 to at least partially occlude the SVC simultaneouslyas controller 217 actuates pump 214 to pump blood from the leftventricle to the aorta.

FIG. 50 presents results obtained in an animal model, which demonstratesleft ventricular (“LV”) total volume—LV pressure for (1) a baselinemodel; (2) an LVAD model; and (3) an LVAD+SVC occlusion system model. Asis evident from comparing model (3) to models (1) and (2), a reductionin cardiac preload (“CP”) and left ventricular wall tension (“LVWT”)results from use of a SVC occlusion system as described herein incombination with a trans-valvular LVAD (Impella CP® heart pump availablefrom Abiomed® of Danvers, Mass.), showing improved functionality andefficiency in pre-load reduction caused by the LVAD. In addition, thetrans-valvular LVAD may be operated at a lower rate of pumping whileachieving sufficient systemic cardiovascular support, thus reducing thepotential for adverse events related to the LVAD.

Referring now to FIG. 51 an SVC occlusion system in combination with atrans-valvular RVAD is described. For example, SVC occlusion system 30having flow limiting element 32 at distal portion 34 of catheter 31 maybe positioned within the SVC, as described above, to at least partiallyocclude the SVC intermittently, and RVAD system 218 may be positioneddistal to flow limiting element 32 on catheter 31, offering fullhemodynamic support. In one example, RVAD system 218 is an Impella RP®heart pump available from Abiomed® of Danvers, Mass. RVAD system 218illustratively includes inflow end 219, outflow end 220, impeller pump221, and anchor 222, disposed on a distal portion of catheter 223. Forexample, anchor 222 may be a pigtail anchor. During operation, outflowend 220 is positioned in the pulmonary artery and inflow end 219 ispositioned in the SVC, distal to flow limiting element 32. As impellerpump 221 is actuated, blood within the SVC is pumped through inflow end219 and expelled into the pulmonary artery via outflow end 220, therebymimicking the natural pathway of blood flow and unloading the rightventricle. For example, impeller pump 221 may deliver up to 5.0 L/min offorward blood flow from the SVC to the pulmonary artery. As will beunderstood by one having ordinary skill in the art, any suitable pumpmay be used.

In addition, controller 33 may be configured to be operatively coupledto RVAD system 218 to actuate pump 221 to pump blood from the SVC to thepulmonary artery, thereby unloading the right ventricle. Thus,controller 33 may simultaneously actuate flow limiting element 32 to atleast partially occlude the SVC and pump 221 to pump blood from the SVCto the pulmonary artery.

Referring now to FIG. 52 an SVC occlusion system in combination with analternative trans-valvular RVAD is described. For example, SVC occlusionsystem 30 having flow limiting element 32 at distal portion 34 ofcatheter 31 may be positioned within the SVC, as described above, to atleast partially occlude the SVC intermittently, and RVAD system 218 maybe positioned in the right side of the heart, offering full hemodynamicsupport. In one example, RVAD system 218 is an Impella CP® heart pumpavailable from Abiomed® of Danvers, Mass. RVAD system 218 illustrativelyincludes inflow end 219, outflow end 220, impeller pump 221, and anchor222, disposed on a distal portion of catheter 223. For example, anchor222 may be a pigtail anchor. During operation, inflow end 219 ispositioned in the inferior vena cava (IVC) and outflow end 220 ispositioned in the pulmonary artery. As impeller pump 221 is actuated,blood within the IVC is pumped through inflow end 219 and expelled intothe pulmonary artery via outflow end 220, thereby mimicking the naturalpathway of blood flow, unloading the right ventricle. For example,impeller pump 221 may deliver up to 5.0 L/min of forward blood flow fromthe IVC to the pulmonary artery. As will be understood by one havingordinary skill in the art, any suitable pump may be used.

In addition, RVAD system 218 includes controller 224 configured to beoperatively coupled to catheter 223 to actuate pump 221 to pump bloodfrom the IVC to the pulmonary artery, thereby unloading the rightventricle. Controller 224 and controller 33 may be the same and/orincorporated into the same housing unit, such that a single controlleris operatively coupled to flow limiting element 32 and pump 221.Controller 33 may actuate flow limiting element 32 to at least partiallyocclude the SVC simultaneously as controller 224 actuates pump 221 topump blood from the IVC to the pulmonary artery.

Referring now to FIG. 53 an SVC occlusion system in combination with atransapical LVAD is described. For example, SVC occlusion system 30having flow limiting element 32 at distal portion 34 of catheter 31 maybe positioned within the SVC, as described above, to at least partiallyocclude the SVC intermittently, and LVAD system 225 may be positionedtransapically in the left side of the heart, offering full hemodynamicsupport. In one example, LVAD system 225 is an HeartWare™ HVAD™ Systemavailable from HeartWare, Inc. of Miami Lakes, Fla. LVAD system 225illustratively includes inflow end 226, outflow end 227, and pump 228,implanted near the apex of the left ventricle. During operation, inflowend 226 is positioned in the left ventricle and outflow end 227 ispositioned in the ascending aorta. As pump 228 is actuated, blood withinthe left ventricle is pumped through inflow end 226 and expelled intothe aorta via outflow end 227, thereby mimicking the natural pathway ofblood flow, unloading the left ventricle, and increasing coronary andsystemic perfusion. As will be understood by one having ordinary skillin the art, any suitable pump may be used.

In addition, LVAD system 225 includes controller 229 configured to beoperatively coupled to pump 228 to actuate pump 228 to pump blood fromthe left ventricle to the aorta. Controller 229 and controller 33 may bethe same and/or incorporated into the same housing unit, such that asingle controller is operatively coupled to flow limiting element 32 andpump 228. Controller 33 may actuate flow limiting element 32 to at leastpartially occlude the SVC as controller 229 simultaneously actuates pump228 to pump blood from the left ventricle to the aorta.

Referring now to FIG. 54 an SVC occlusion system in combination with anintra-aortic balloon pump (IABP) is described. For example, SVCocclusion system 30 having flow limiting element 32 at distal portion 34of catheter 31 may be positioned within the SVC, as described above, toat least partially occlude the SVC intermittently, and IABP 230 may bepositioned the descending aorta. IABP may include flow limiting element231 and catheter 232 coupled to flow limiting element 231. Flow limitingelement 231 illustratively comprises a balloon capable of transitioningbetween a contracted state, allowing transluminal placement, and anexpanded, deployed state. Flow limiting element 231 is preferably sizedand shaped so that it partially or fully occludes flow in the aorta inthe expanded state. Catheter 232 may be coupled to controller 33 at aproximal end. Controller 33, houses drive mechanism 36 for independentlyactuating flow limiting element 32 and flow limiting element 231. Asshown in FIG. 54 , flow limiting element 231 and flow limiting element32 may be coupled to the same controller such that a single controlleris operatively coupled to flow limiting element 32, flow limitingelement 231, and pump 221. However, it is understood that flow limitingelement 32 and flow limiting element 231 may be coupled to differentcontrollers and/or different pumps. During operation, flow limitingelement 231 will be positioned within the descending aorta and willintermittently inflate and deflate. Inflation may be timed to coincidewith diastole and deflation timed to coincide with systole. As flowlimiting element 231 deflates, a suction effect is created in the aorta,facilitating the transfer of blood from the left ventricle to the aortaduring systole.

The combination of the SVC occlusion system with a VAD, RVAD or LVAD mayreduce the required flow rate of the VAD to achieve the same hemodynamicresponse in the patient. This would lower the required speed of thepump, thereby reducing the potential complications associated with thehigher speed of the pump required to generate higher flow rates.Further, intermittent occlusion of the SVC following implantation of thepump may help unload the right ventricle while the LVAD is being broughtup to operational speed.

It is to be understood that the foregoing description is intended toillustrate and not to limit the scope of the invention, which is definedby the scope of the appended claims. Other embodiments are within thescope of the following claims.

What is claimed is:
 1. A method for unloading of cardiac preload andafterload, the method comprising: pumping blood within a patient using acardiac assist device to reduce cardiac afterload; positioning a flowlimiting element at a superior vena cava (SVC) of the patient; and atleast partially occluding the SVC via the flow limiting element overmultiple cardiac cycles to reduce cardiac preload.
 2. The method ofclaim 1, wherein positioning the flow limiting element comprisesintravascularly positioning the flow limiting element disposed on acatheter within the SVC, and wherein the at least partially occludingthe SVC comprises expanding the flow limiting element.
 3. The method ofclaim 2, further comprising contracting the flow limiting element withinthe SVC, the expanding and the contracting reducing the cardiac preload.4. The method of claim 3, further comprising repeating the expanding andthe contracting over a course of a treatment.
 5. The method of claim 1,wherein the at least partially occluding the SVC via the flow limitingelement comprises fully occluding the SVC via the flow limiting element.6. The method of claim 1, wherein the cardiac assist device is aventricular assist device (VAD).
 7. The method of claim 6, wherein theVAD is a left ventricular assist device (LVAD).
 8. The method of claim1, wherein the cardiac assist device is an intra-aortic balloon pump(IABP).
 9. The method of claim 3, wherein expanding the flow limitingelement comprises expanding the flow limiting element to at leastpartially occlude the SVC for a first predetermined time interval andthe contracting comprises contracting the flow limiting element for asecond predetermined time interval over multiple cardiac cycles.
 10. Themethod of claim 9, wherein the first predetermined time interval is atleast five times greater than the second predetermined time interval.11. The method of claim 9, wherein the first predetermined time intervalis 5-20 minutes and the second predetermined time interval is 10-100seconds.
 12. The method of claim 1, wherein the SVC is at leastpartially occluded for up to 95% of an hour.
 13. The method of claim 1,wherein the at least partially occluding further reduces the patient'sdiastolic volume and improves cardiac performance as measured by atleast one of: reduced cardiac filling pressures, increased leftventricular relaxation, increased left ventricular capacitance,increased left ventricular stroke volume, increased lusitropy, reducedleft ventricular stiffness or reduced cardiac strain.
 14. The method ofclaim 1, wherein the at least partially occluding creates a negativepressure sink in a right atrium of the patient, accelerating flow from arenal vein, thereby enhancing renal decongestion and promoting bloodflow across a kidney of the patient.
 15. The method of claim 1, furthercomprising monitoring pressure differential across the flow limitingelement in the SVC indicative of an amount or degree of occlusion in theSVC.
 16. The method of claim 1, further comprising: outputting a firstpressure signal via a first pressure sensor disposed proximal to theflow limiting element; outputting a second pressure signal via a secondpressure sensor disposed distal to the flow limiting element; anddetermining pressure in the SVC based on the first pressure signal orthe second pressure signal or both.
 17. The method of claim 1, furthercomprising determining pressure in the SVC.
 18. The method of claim 3,wherein the expanding and the contracting are caused by a controlleroperatively coupled to the flow limiting element.
 19. The method ofclaim 18, further comprising implanting the controller.
 20. The methodof claim 1, wherein the flow limiting element is a balloon.
 21. Themethod of claim 1, further comprising transitioning a relief valvecoupled to the flow limiting element from a closed position to an openposition to permit fluid to flow through the SVC to a right atrium ofthe patient.
 22. The method of claim 21, wherein transitioning therelief valve from the closed position to the open position comprisestransitioning the relief valve from the closed position to the openposition at a pressure between 30-60 mmHg.